title: Relapse pattern and second-line treatment following multimodality treatment for malignant pleural mesothelioma.
abstract: OBJECTIVE
  To analyse the relapse pattern and influence of second-line treatment after recurrence of malignant pleural mesothelioma (MPM) in patients who had previously undergone multimodality treatment.
  
  
  METHODS
  Between September 1999 and December 2013, 136 patients underwent macroscopic complete resection (MCR) by extrapleural pneumonectomy after induction chemotherapy for MPM. We analysed 106 patients who presented with recurrent disease until October 2014. Data were retrieved from our mesothelioma database, with additional information regarding precise localization gathered by reviewing the imaging and medical records.
  
  
  RESULTS
  The overall recurrence rate was 78% (106/136 patients). The median freedom from recurrence was 9 months after surgery [95% confidence interval (95% CI) 7-10]. Local recurrence only was observed in 33 patients (31%), distant metastases only in 27 patients (26%) and simultaneous distant and local recurrence in 46 patients (43%). Local recurrence was observed significantly less frequently in patients having received adjuvant radiotherapy (19 vs 47%, P = 0.003), but there was no significant impact on overall survival (OS) [radiation: 22 months (95% CI 19-24); no-radiation: 23 months (95% CI 18-27), P = 0.6]. The median OS was 22 months (95% CI 21-24), median post-recurrence survival (PRS) was 7 months (95% CI 5-9) and patients with local recurrence only survived significantly longer (12 months, 95% CI 8-16) compared with patients with distant recurrence only (5 months, 95% CI 2-8) or distant plus local relapse (6 months, 95% CI 3-9; P = 0.04). A total of 78 patients received a second-line therapy after tumour recurrence: chemotherapy (n = 48), local radiotherapy (n = 9), surgery (n = 10) or a combination thereof (n = 11). Patients undergoing second-line treatment survived significantly longer compared with patients not receiving therapy (P < 0.0005). The median PRS after surgery was significantly longer than that of patients receiving chemo-, radio- or chemo-radiotherapy (P = 0.04).
  
  
  CONCLUSIONS
  Local recurrence of MPM remains the most frequent type of relapse even after multimodality treatment including MCR. In the present cohort, active treatment seems beneficial to the patient since surgical excision of local tumour relapse has good long-term outcome in selected patients. Thus, second-line treatment may prolong PRS; however, these results need to be confirmed in a prospective manner.
authors.affiliation: Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Arthur
authors.initials: A
authors.lastname: Kostron
authors.affiliation: Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Martina
authors.initials: M
authors.lastname: Friess
authors.affiliation: Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Ornella
authors.initials: O
authors.lastname: Crameri
authors.affiliation: Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Ilhan
authors.initials: I
authors.lastname: Inci
authors.affiliation: Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Didier
authors.initials: D
authors.lastname: Schneiter
authors.affiliation: Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Sven
authors.initials: S
authors.lastname: Hillinger
authors.affiliation: Department of Oncology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Rolf
authors.initials: R
authors.lastname: Stahel
authors.affiliation: Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Walter
authors.initials: W
authors.lastname: Weder
authors.affiliation: Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland isabelle.schmitt-opitz@usz.ch.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Opitz
mesh_terms: D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000453:epidemiology / Q000401:mortality / Q000628:therapy; D008297:Male; D008654:Mesothelioma / Q000453:epidemiology / Q000401:mortality / Q000628:therapy; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000401:mortality / Q000628:therapy; D012189:Retrospective Studies; D016896:Treatment Outcome
keywords: Distant failure; Local recurrence; Malignant pleural mesothelioma; Multimodality treatment; Second-line therapy