This document discusses expanding the use of radiation therapy for malignant pleural mesothelioma. It summarizes the current approaches and outcomes for three scenarios: post-pneumonectomy radiation, post-pleurectomy radiation, and radiation for unresectable disease. For each scenario, intensity modulated radiation therapy (IMRT) to the pleura is presented as a way to improve local tumor control and survival rates compared to conventional radiation techniques, though there are risks of fatal pneumonitis that require careful patient selection and planning. Overall the document evaluates the potential benefits of pleural IMRT across different disease stages while also acknowledging toxicity challenges.

1. 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

2. Scenarios
Pneumonectomy Pleurectomy Unresectable
Post-op RT “Definitive” RT
Post-op RT vs. no further vs. no further
treatment treatment

3. Scenarios
Pneumonectomy Pleurectomy Unresectable
Post-op RT “Definitive” RT
Post-op RT vs. no further vs. no further
treatment treatment

4. RT after Pneumonectomy (EPP)
 Conventional RT
– Severe toxicity rare
– Acceptable local control
(10 – 40%)
 IMRT
– Potentially improved local
control
– Severe toxicity too
common

5. Toxicity of IMRT
Institution Median Fatal
Radiation Pneumonitis
Dose (Gy)
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

6. 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

7. Scenarios
Pneumonectomy Pleurectomy Unresectable
Post-op RT “Definitive” RT
Post-op RT vs. no further vs. no further
treatment treatment
Pleural Radiation Therapy

8. Pleural RT with Intact Lungs
A big challenge due
to the risk of
pneumonitis
 Conventional
technique had
limited effectiveness

9. 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)

10. Contouring the Target

13. 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

14. 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

15. Patient Characteristics
N (%) N (%)
Age Histological
-Median 67 Subtype
-Range 42 - 82 -Epithelioid 28 (78)
Gender -Sarcomatoid 2 (6)
-Male 29 (81) -Mixed 6 (17)
-Female 7 (19) Stage
Surgery -I 2 (6)
-P/D or P 20 (56) -II 10 (28)
-Nonoperative 16 (44) -III 12 (33)
-IV 12 (33)
Chemotherapy
-Yes 32 (89) Laterality
-No 4 (11) -Right 20 (56)
-Left 16 (44)

16. 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

17. Scenarios
EPP P/D Unresectable
Post-op RT “Definitive” RT
Post-op RT vs. no further vs. no further
treatment treatment

18. 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)

19. 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%

20. Scenarios
Pneumonectomy Pleurectomy Unresectable
Post-op RT “Definitive” RT
Post-op RT vs. no further vs. no further
treatment treatment

21. 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

22. Pleural IMRT for Unresectable MPM
 Sixteenpatients
 Median overall survival was 17 months
– 1 year survival rate was 69%
– 2 year survival rate was 28%

23. Patient Example - Unresectable
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.
Feb 2007 Diagnosed May 2007 After four cycles Nov 2007 After 5040 cGy
Unresectable MPM of chemotherapy – pleural IMRT. Response and
No response less pain

24. 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

25. Pulmonary Toxicity

26. Conclusions
Pneumonectomy Pleurectomy Unresectable
Post-op RT “Definitive” RT
Post-op RT vs. no further vs. no further
treatment treatment
Conventional Consider pleural Consider pleural
RT (IMRT with IMRT to improve IMRT to prolong
caution) local control palliation

27. Acknowledgments
 ValerieRusch, Raja Flores
 Lee Krug
 Ellen Yorke
 Andreas Rimner