Trimodality treatment of malignant pleural mesothelioma

Our plain-English summary of Trimodality treatment of malignant pleural mesothelioma, by H.F. Batirel, M. Metintas, H.B. Caglar, et al (Journal of Thoracic Oncology, 2008).

The study

• Authors: H.F. Batirel, M. Metintas, H.B. Caglar, B. Yildizeli, T. Lacin, K. Bostanci, A.G. Akgul, S. Evman, M. Yuksel
• Journal: Journal of Thoracic Oncology
• Published: 2008;3(5):499-504
• Cited by: 56 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Multimodality treatment has achieved significant success in local control and treatment of early-stage malignant pleural mesothelioma patients. However, its favorable effect on survival is questionable.

Methods: We have instituted a trimodality treatment protocol consisting of extrapleural pneumonectomy, adjuvant high-dose (54 Gy) hemithoracic irradiation, and platin-based chemotherapy in a multi-institutional setting. Preoperative pulmonary function tests, echocardiogram, chest computed tomography, and magnetic resonance imaging scans were performed in all patients. Twenty patients have been treated with this protocol during 2003-2007. Seventeen had a history of environmental asbestos/erionite exposure. Clinical stages were T1-3N0-2.

Results: Median age was 56 (41-70, 8 female). There was one postoperative mortality (% 5) due to ARDS. Morbidity occurred in 11 patients (% 55). Histology was epithelial in 17, mixed in 2, and sarcomatoid in 1. Sixteen patients underwent extrapleural pneumonectomy. Microscopic margin positivity was present in 14 patients with macroscopic complete resection. Twelve patients completed all three treatments. Median follow-up was 16 months (1-43). Overall median survival was 17 months (24% at 2 years). Eight patients had extrapleural lymph node involvement (internal mammary [n = 3], subcarinal [n = 2], pulmonary ligament [n = 1], diaphragmatic [n = 1], subaortic [n = 1]). There was better survival in patients without lymph node metastasis (24 versus 13 months median survival, p = 0.052). Currently, 7 patients are alive, 6 without recurrence, and 2 patients at 40 and 45 months.

Conclusions: Trimodality treatment in malignant pleural mesothelioma seems to prolong survival in patients without lymph node metastasis. Novel techniques are needed for preoperative assessment of extrapleural lymph nodes.

In plain English

This was a small phase II study at Turkish university hospitals, run from 2003 to 2007. It tested a three-part treatment for malignant pleural mesothelioma: extrapleural pneumonectomy (removing the pleura, lung, diaphragm and pericardium), then high-dose (54 Gy) radiation to that side of the chest, then cisplatin-based chemotherapy. Of 37 patients evaluated, 20 were enrolled. Most had environmental exposure (17 in the abstract, 16 in the patient table); three had erionite exposure and the others asbestos. Sixteen had the surgery and 12 completed all three treatments. One patient died in hospital and 11 (55%) had complications. Median survival was 17.2 months for all 20 patients and 23.9 months for those completing treatment. Eight patients had cancer in lymph nodes outside the pleura. Their median survival was 13.3 months, against 23.9 months without such spread, a difference the authors called very close to significance (p of 0.052). The authors concluded the treatment seems to prolong survival in patients without lymph node metastasis and that its benefit with lymph node involvement is questionable. They noted the small number of patients.

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: Prospective phase II treatment protocol (case series), multi-institutional, designed to enroll 20 patients
• Who was studied: 20 patients with histologically proven malignant pleural mesothelioma, enrolled from 37 evaluated for multimodality treatment, 2003 to 2007, at Marmara University (Istanbul) and Osmangazi University (Eskisehir), Turkey. 12 male, 8 female; median age 56 (range 41 to 70). Histology per the patient table: 17 epithelial, 2 mixed, 1 sarcomatoid.
• Exposure: The patient table lists environmental exposure in 16 (80%) and other exposure in 4 (20%), with three patients having erionite exposure and the others asbestos exposure; the abstract says 17 had environmental asbestos/erionite exposure. Asbestos fiber types are not specified. The treatment studied was extrapleural pneumonectomy, then hemithoracic radiation (minimum 54 Gy), then cisplatin with gemcitabine (2003 to 2005) or cisplatin with pemetrexed (from 2005).
• Main results:
  • Extrapleural pneumonectomy was performed in 16 of the 20 patients; it could not be performed in 4.
  • There was 1 in-hospital death (5%), from ARDS and sepsis after re-exploration for a ruptured diaphragmatic mesh. 11 patients (55%) developed complications, all among those who underwent extrapleural pneumonectomy.
  • Only 2 of the patients who underwent extrapleural pneumonectomy had microscopic complete resection; 14 had microscopic tumor at the margins.
  • 12 of the 16 patients who underwent extrapleural pneumonectomy (75%) completed the full trimodality protocol.
  • Radiation (median total dose 54 Gy, range 52 to 63 Gy) was reported as well tolerated, without treatment interruptions. Myelosuppression, the most frequent chemotherapy adverse event, occurred in 12% of all cycles. There were no chemotherapy-related deaths.
  • Median survival was 17.2 months in the whole cohort (n = 20), 19.6 months in patients who underwent extrapleural pneumonectomy (n = 16), and 23.9 months in those who completed trimodality treatment (n = 12). The authors report no statistically significant difference (p = 0.52).
  • Eight patients had extrapleural lymph node metastasis. Their median survival was 13.3 months, compared with 23.9 months in patients without lymph node metastasis.
  • The authors described this lymph node survival difference as very close to significance (p = 0.052), meaning it did not reach conventional statistical significance.
  • After excluding two patients with mixed histology, the 3-year survival rate was 56% (n = 6) among patients with epithelial histology and no lymph node metastasis; median survival in this group was not reached.
  • 9 patients who underwent extrapleural pneumonectomy had recurrence, at a median of 10 months (range 2 to 26). 5 of these recurrences were in patients with extrapleural lymph node involvement.
• The authors' conclusion: The authors concluded that trimodality treatment seems to prolong survival in malignant pleural mesothelioma patients without lymph node metastasis, that its benefit in patients with extrapleural lymph node involvement is questionable, and that better methods for preoperative staging of extrapleural lymph nodes are needed.
• Limitations the authors state:
  • The number of patients treated with the protocol was limited.
  • The treatment is very difficult for patients and usually takes 4 to 6 months to complete.
  • The chemotherapy regimens were not standard: the regimen was changed during the study.
  • There is not enough data on how accurately PET scans identify extrapleural lymph node metastasis.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Extrapleural Pneumonectomy (EPP), Chemotherapy, Pulmonary Function Test (PFT), Echocardiogram, erionite, Histology, Sarcomatoid.

Related studies

• Trimodality Treatment of Malignant Pleural Mesothelioma: An Institutional Review — M. Kapeles, M.F. Gensheimer, et al. (2018)
• Miliary mesothelioma: a new clinical and radiological presentation in mesothelioma patients with prolonged survival after trimodality therapy — L. Purek, S. Laroumagne, et al. (2011)
• Integrated positron emission tomography-computed tomography does not accurately stage intrathoracic disease of patients undergoing trimodality therapy for malignant pleural mesothelioma — J. Pilling, J.A. Dartnell, et al. (2010)
• Trimodality management of malignant pleural mesothelioma — G. Maggi, C. Casadio, et al. (2001)
• Trimodality strategy for treating malignant pleural mesothelioma: results of a feasibility study of induction pemetrexed plus cisplatin followed by extrapleural pneumonectomy and postoperative hemithoracic radiation (Japan Mesothelioma Interest Group 0601 Trial) — S. Hasegawa, M. Okada, et al. (2016)
• Patterns of failure after trimodality therapy for malignant pleural mesothelioma — E.H. Baldini, A. Recht, et al. (1997)

Browse more research in Journal of Thoracic Oncology, or return to medical research.