Fatal pneumonitis associated
with intensity-modulated radiation therapy for mesothelioma
Fatal pneumonitis associated with intensity-modulated radiation therapy
for mesothelioma
Allen AM, Czerminska M, Janne PA, Sugarbaker DJ, Bueno R, Harris JR, Court
L, Baldini EH.
Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham
and Women's Hospital, Boston, MA, USA.
PURPOSE: To describe the initial experience at Dana-Farber Cancer
Institute/Brigham and Women's Hospital with intensity-modulated radiation
therapy (IMRT) as adjuvant therapy after extrapleural pneumonectomy (EPP) and
adjuvant chemotherapy.
METHODS AND MATERIALS: The medical records of patients treated with
IMRT after EPP and adjuvant chemotherapy were retrospectively reviewed. IMRT was
given to a dose of 54 Gy to the clinical target volume in 1.8 Gy daily
fractions. Treatment was delivered with a dynamic multileaf collimator using a
sliding window technique. Eleven of 13 patients received heated intraoperative
cisplatin chemotherapy (225 mg/m(2)). Two patients received neoadjuvant
intravenous cisplatin/pemetrexed, and 10 patients received adjuvant
cisplatin/pemetrexed chemotherapy after EPP but before radiation therapy. All
patients received at least 2 cycles of intravenous chemotherapy. The
contralateral lung was limited to a V20 (volume of lung receiving 20 Gy or more)
of 20% and a mean lung dose (MLD) of 15 Gy. All patients underwent
fluorodeoxyglucose positron emission tomography (FDG-PET) for staging, and any
FDG-avid areas in the hemithorax were given a simultaneous boost of radiotherapy
to 60 Gy. Statistical comparisons were done using two-sided t test.
RESULTS: Thirteen patients were treated with IMRT from December 2004
to September 2005. Six patients developed fatal pneumonitis after treatment. The
median time from completion of IMRT to the onset of radiation pneumonitis was 30
days (range 5-57 days). Thirty percent of patients (4 of 13) developed acute
Grade 3 nausea and vomiting. One patient developed acute Grade 3
thrombocytopenia. The median V20, MLD, and V5 (volume of lung receiving 5 Gy or
more) for the patients who developed pneumonitis was 17.6% (range, 15.3-22.3%),
15.2 Gy (range, 13.3-17 Gy), and 98.6% (range, 81-100%), respectively, as
compared with 10.9% (range, 5.5-24.7%) (p = 0.08), 12.9 Gy (range, 8.7-16.9 Gy)
(p = 0.07), and 90% (range, 66-98.3%) (p = 0.20), respectively, for the patients
who did not develop pneumonitis.
CONCLUSIONS: Intensity-modulated RT treatment for mesothelioma after
EPP and adjuvant chemotherapy resulted in a high rate of fatal pneumonitis when
standard dose parameters were used. We therefore recommend caution in the
utilization of this technique. Our data suggest that with IMRT, metrics such as
V5 and MLD should be considered in addition to V20 to determine tolerance levels
in future patients.