title: Impact of induction therapy on postoperative outcome after extrapleural pneumonectomy for malignant pleural mesothelioma: does induction-accelerated hemithoracic radiation increase the surgical risk?
abstract: OBJECTIVE
  Patients with malignant pleural mesothelioma (MPM) eligible for extrapleural pneumonectomy (EPP) may benefit from induction chemotherapy (CT) as historically described, or from induction-accelerated hemithoracic intensity-modulated radiation therapy (IMRT) as a potential alternative. However, the impact of the type of induction therapy on postoperative morbidity and mortality remains unknown.
  
  
  METHODS
  We performed a retrospective study including every patient who underwent EPP for MPM in our institution between January 2001 and December 2014. Patients without induction treatment (n = 7) or undergoing both induction CT and IMRT (n = 2) were then excluded. The remaining patients (study group) were divided according to the type of induction treatment in Group 1-CT and Group 2-IMRT. Major complications were defined by complications of Grade 3 or higher according to the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0 guidelines. Red blood cell (RBC) transfusion was analysed as a number of packs, and dichotomized as <3 vs ≥3 packs. Plasma and platelet transfusion were analysed as a number of units, and dichotomized as no transfusion versus any plasma or platelet transfusion.
  
  
  RESULTS
  Altogether, 126 patients (mean age 61.3 ± 8.1 years, males 82.5%, right side 60.3%, 90-day mortality rate 4.8%) accounted for the study group. Sixty-four patients were included in Group 1-CT and 62 patients were included in Group 2-IMRT. When compared with Group 1-CT, Group 2-IMRT was characterized by older patients (59.3 ± 9.2 vs 63.3 ± 8.3 years, P = 0.012), more right-sided resections (46.8 vs 74.1%, P = 0.003), more advanced disease (pathological stage IV: 28.1 vs 53.2%, P = 0.007), less RBC transfusions (5.1 ± 3.0 vs 3.0 ± 2.4 packs, P < 0.001), less plasma or platelet transfusions (31.2 vs 9.6%, P = 0.005) and similar rate of major complications (29.6 vs 35.4%, P = 0.614). The 90-day mortality rate was 6.2% in Group 1-CT (n = 4) and 3.2% in Group 2-RT (n = 2, P = 0.680). Induction with IMRT was significantly associated with a decreased risk of transfusion with RBCs [odds ratio (OR) = 0.10, 95% confidence interval (CI) 0.04-0.23, P < 0.001] as well as plasma and platelets (OR = 0.25, 95% CI 0.086-0.67, P = 0.008).
  
  
  CONCLUSIONS
  In this large single-centre series of EPP for MPM, the implementation of induction IMRT was not associated with any significant increase in the surgical risks above and beyond induction CT. The switch from induction CT to induction IMRT was associated with resection in older patients with more advanced tumours, less transfusion requirements, comparable postoperative morbidity and 90-day mortality.
authors.affiliation: Division of Thoracic Surgery, Toronto General Hospital and Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Mordant
authors.affiliation: Department of Anesthesia and Pain Management, Toronto General Hospital and Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: McRae
authors.affiliation: Department of Radiation Oncology, Toronto General Hospital and Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Cho
authors.affiliation: Division of Thoracic Surgery, Toronto General Hospital and Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
authors.affiliation: Division of Thoracic Surgery, Toronto General Hospital and Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Waddell
authors.affiliation: Department of Medical Oncology, Toronto General Hospital and Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
authors.forename: Ronald
authors.initials: R
authors.lastname: Feld
authors.affiliation: Division of Thoracic Surgery, Toronto General Hospital and Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada marc.deperrot@uhn.ca.
authors.forename: Marc
authors.initials: M
authors.lastname: de Perrot
mesh_terms: D000368:Aged; D001803:Blood Transfusion / Q000379:methods; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D008654:Mesothelioma / Q000473:pathology / Q000628:therapy*; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000379:methods; D009367:Neoplasm Staging; D010997:Pleural Neoplasms / Q000473:pathology / Q000628:therapy*; D011013:Pneumonectomy / Q000009:adverse effects* / Q000379:methods; D011379:Prognosis; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012189:Retrospective Studies; D016896:Treatment Outcome
keywords: Chemotherapy; Induction therapy; Mesothelioma; Radiation therapy