A feasibility study evaluating Surgery for Mesothelioma After Radiation Therapy: the "SMART" approach for resectable malignant pleural mesothelioma.
BACKGROUND
We developed an innovative approach for malignant pleural mesothelioma (MPM) with a short accelerated course of high-dose hemithoracic intensity-modulated radiation therapy (IMRT) followed by extrapleural pneumonectomy (EPP). This phase I/II study assessed the feasibility of Surgery for Mesothelioma After Radiation Therapy (SMART).


METHODS
All resectable clinical T1-3N0M0 histologically proven, previously untreated MPMs were eligible. Patients received 25 Gy in five daily fractions during 1 week to the entire ipsilateral hemithorax with concomitant 5 Gy boost to areas at risk followed by EPP within 1 week of completing neoadjuvant IMRT. Adjuvant chemotherapy was offered to ypN2 patients on final pathologic findings. The primary end point was treatment-related mortality and secondary end points were overall survival, disease-free survival, treatment-related morbidity, and patterns of failure.


RESULTS
Targeted accrual of 25 patients was completed between November 2008 and October 2012. All patients completed SMART. IMRT was well tolerated with no grade 3+ toxicities. EPP was performed 6 ± 2 days after completing IMRT without any perioperative mortality. Thirteen patients developed grade 3+ surgical complications. One patient (4%) died from treatment-related toxicity (empyema) during follow-up. All but one patient had stage III or IV disease on final pathologic findings. Five of 13 ypN2 patients received adjuvant chemotherapy. After a median follow-up of 23 months (range, 6-51), the cumulative 3-year survival reached 84% in epithelial subtypes compared with 13% in biphasic subtypes (p = 0.0002).


CONCLUSIONS
SMART is feasible in resectable MPM patients. This innovative protocol presents encouraging results and supports future studies looking at long-term outcome in patients with epithelial subtypes.
Departments of *Radiation Oncology, †Medical Oncology, and §Pathology, ‡Division of Thoracic Surgery, Princess Margaret Cancer Centre and Toronto General Hospital, University Health Network, University of Toronto, Ontario, Canada.
B C John
BC
Cho
Ron
R
Feld
Natasha
N
Leighl
Isabelle
I
Opitz
Masaki
M
Anraku
Ming-Sound
MS
Tsao
David M
DM
Hwang
Andrew
A
Hope
Marc
M
de Perrot
D000328:Adult; D003131:Combined Modality Therapy; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008654:Mesothelioma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D009367:Neoplasm Staging; D010997:Pleural Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011013:Pneumonectomy; D011379:Prognosis; D011446:Prospective Studies; D050397:Radiotherapy, Intensity-Modulated; D015996:Survival Rate