Expanding the Field of Radiation Therapy for Malignant Pleural Mesothelioma | Mesothelioma Applied Research Foundation

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