Pulmonary toxicity following IMRT after extrapleural pneumonectomy for malignant pleural mesothelioma.
OBJECTIVE
The combination of chemotherapy, surgery, and radiotherapy has improved the prognosis for patients with malignant pleural mesothelioma (MPM). Intensity-modulated radiotherapy (IMRT) has allowed for an increase in dose to the pleural cavity and a reduction in radiation doses to organs at risk. The present study reports and analyses the incidence of fatal pulmonary toxicity in patients treated at Rigshospitalet, Copenhagen.


METHODS
Twenty-six patients were treated with induction chemotherapy followed by extrapleural pneumonectomy and IMRT between April 2003 and April 2006. The entire preoperative pleural surface area was treated to 50 Gy and areas with residual disease or close surgical margins were treated to 60 Gy in 30 fractions.


RESULTS
The main toxicities were nausea, vomiting, esophagitis, dyspnea, and thrombocytopenia. One patient died from an intracranial hemorrhage during severe thrombocytopenia. Four patients (15%) experienced grade 5 lung toxicity, i.e. pneumonitis 19-40 days after the completion of radiotherapy. Patients with pneumonitis had a significantly larger lung volume fraction receiving 10 Gy or more (V10) (median: 60.3%, range 56.4-83.2%) compared to patients without pneumonitis (median: 52.6%, range: 25.6-80.3%) (p=0.02). Mean lung dose (MLD) was also significantly higher in patients who developed pneumonitis (median 13.9 Gy, range: 13.6-14.2 Gy) than in patients who did not (median=12.4 Gy, range: 8.4-15.4 Gy) (p=0.04).


CONCLUSIONS
Significant differences in MLD and V10 for patients with fatal pulmonary toxicity compared to patients without fatal lung toxicity have been demonstrated. Based on the presented data local lung dose constraints have been modified in order to avoid unacceptable toxicity.
Kristensen
Claus Andrup
CA
Department of Oncology, Copenhagen University Hospital/Rigshospitalet, Denmark. claus.andrup.kristensen@rh.regionh.dk
Nøttrup
Trine Juhler
TJ
Berthelsen
Anne Kiil
AK
Kjaer-Kristoffersen
Flemming
F
Ravn
Jesper
J
Sørensen
Jens Benn
JB
Engelholm
Svend-Aage
SA
D000368:Aged; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy / Q000532:radiotherapy* / Q000601:surgery; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000188:drug therapy / Q000532:radiotherapy* / Q000601:surgery; D011013:Pneumonectomy; D011829:Radiation Dosage; D017564:Radiation Pneumonitis; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects*; D016896:Treatment Outcome