Relapse pattern and second-line treatment following multimodality treatment for malignant pleural mesothelioma

Our plain-English summary of Relapse pattern and second-line treatment following multimodality treatment for malignant pleural mesothelioma, by A. Kostron, M. Friess, O. Crameri, et al (European Journal of Cardio-thoracic Surgery, 2016).

The study

• Authors: A. Kostron, M. Friess, O. Crameri, I. Inci, D. Schneiter, S. Hillinger, R. Stahel, W. Weder, I. Opitz
• Journal: European Journal of Cardio-thoracic Surgery
• Published: 2016;49(5):1516-23
• Cited by: 43 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: 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.

© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

In plain English

This retrospective Zurich study looked at 106 patients with malignant pleural mesothelioma whose cancer returned after chemotherapy and extrapleural pneumonectomy (removal of the lung and pleura). It does not discuss asbestos. Recurrence was local only in 33 patients (31%), distant only in 27 (26%) and both in 46 (43%). The operated side of the chest was most often affected (75%). Median time to recurrence after surgery was 9 months (95% CI 7–10). With postoperative radiotherapy, local-only recurrence was less frequent (19% vs 47%) and distant-only more frequent (36% vs 13%). Median overall survival did not differ significantly: 22 months (95% CI 19–24) vs 23 (18–27), P = 0.6. Median survival after recurrence was 7 months (95% CI 5–9): 12 (8–16) for local-only, 5 (2–8) for distant-only and 6 (3–9) for both (P = 0.04). It was 10 months (8–11) for 78 patients given second-line treatment versus 2 (0–5) for 28 untreated patients. The 16 repeat-surgery patients survived a median 16 months (9–24) from recurrence. The authors cautioned that selection bias may explain these differences and called for prospective studies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective analysis of a single-institution mesothelioma database
• Who was studied: 106 patients (93 men, 13 women; median age at surgery 61) with malignant pleural mesothelioma at University Hospital Zurich, Switzerland. All had recurrent disease after induction chemotherapy and extrapleural pneumonectomy. Operations took place between 1999 and 2013, with follow-up to October 2014. They were drawn from 136 patients analysed for recurrence.
• Exposure: Not an asbestos-exposure study. It studied multimodality treatment: induction chemotherapy (platinum/gemcitabine or platinum/pemetrexed), extrapleural pneumonectomy, adjuvant radiotherapy in 59 patients, and second-line treatment after recurrence (chemotherapy, radiotherapy, repeat surgery, or combinations).
• Main results:
  • Among the 106 patients with recurrence: local only 33 (31%), distant only 27 (26%), local plus distant 46 (43%).
  • The ipsilateral hemithorax (the operated side of the chest) was the most frequent recurrence site (79 patients, 75%), followed by the abdomen (53 patients, 50%).
  • Median freedom from recurrence was 9 months after surgery (95% CI 7 to 10). In multivariate analysis, pathological IMIG stage remained a prognostic factor for longer freedom from recurrence (P = 0.001).
  • Local-only recurrence occurred in 11 patients (19%) given adjuvant radiotherapy versus 22 patients (47%) not given it (P = 0.003).
  • Distant-only recurrence occurred in 21 patients (36%) given radiotherapy versus 6 (13%) not given it (P = 0.008).
  • Median overall survival was 22 months (95% CI 19 to 24) with radiotherapy and 23 months (95% CI 18 to 27) without it. The difference was not statistically significant (P = 0.6).
  • Median post-recurrence survival for all patients was 7 months (95% CI 5 to 9).
  • Median post-recurrence survival by recurrence site: local only 12 months (95% CI 8 to 16); distant only 5 months (95% CI 2 to 8); both 6 months (95% CI 3 to 9); P = 0.04.
  • Median post-recurrence survival was 10 months (95% CI 8 to 11) in the 78 patients given any second-line treatment versus 2 months (95% CI 0 to 5) in the 28 patients not treated (P less than 0.0005).
  • Median post-recurrence survival was 16 months (95% CI 9 to 24) for the 16 patients who had repeat surgery, versus 9 months (95% CI 7 to 12) for the 62 given other second-line treatment.
  • Two of the 3 patients who had contralateral partial pleurectomy (surgery on the opposite side of the chest) died in the early postoperative period.
• The authors' conclusion: The authors concluded that the ipsilateral hemithorax remains the main recurrence site after extrapleural pneumonectomy. They found that adjuvant radiotherapy may reduce local recurrence but has no influence on overall survival, and that local-only recurrence has a better prognosis than distant relapse. In their view, second-line treatment, especially repeat surgery with or without radiotherapy, may give favourable outcomes in selected patients, while contralateral pleurectomy is not recommended. Because of selection bias, they said the effect of second treatment must be confirmed by prospective studies.
• Limitations the authors state:
  • Retrospective design, and selection bias in who received each treatment.
  • The added effect of second treatment cannot be separated out, because patient data and information on why a second treatment was given are incomplete.
  • Quality-of-life data were not assessed for the whole cohort and were excluded.
  • Patients treated with pleurectomy/decortication (15 patients) were not included.
  • With imaging every 4 to 6 months, the 9-month median time to recurrence is only an approximation.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Extrapleural Pneumonectomy (EPP), Chemotherapy, Mesothelioma, confidence interval, Overall Survival, Second-Line Therapy.

Related studies

• Patterns of disease progression on 18F-fluorodeoxyglucose positron emission tomography-computed tomography in patients with malignant pleural mesothelioma undergoing multimodality therapy with pleurectomy/decortication — A. Bille, S. Chicklore, et al. (2013)
• Pattern of failure after adjuvant radiotherapy following extrapleural pneumonectomy of pleural mesothelioma in the SAKK 17/04 trial — O. Riesterer, I.F. Ciernik, et al. (2019)
• A New Prognostic Score Supporting Treatment Allocation for Multimodality Therapy for Malignant Pleural Mesothelioma: A Review of 12 Years' Experience — I. Opitz, M. Friess, et al. (2015)
• Updated patterns of failure after multimodality therapy for malignant pleural mesothelioma — E.H. Baldini, W.G. Richards, et al. (2015)
• Life after first-line chemotherapy in malignant pleural mesothelioma: a North-East England experience — J. Steer, G. Bough, et al. (2010)
• Local recurrence model of malignant pleural mesothelioma for investigation of intrapleural treatment — I. Opitz, D. Lardinois, et al. (2007)

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