Diaphragm and lung-preserving surgery with hyperthermic chemotherapy for malignant pleural mesothelioma: A 10-year experience

Our plain-English summary of Diaphragm and lung-preserving surgery with hyperthermic chemotherapy for malignant pleural mesothelioma: A 10-year experience, by M.C. Ambrogi, P. Bertoglio, V. Aprile, et al (The Journal of Thoracic and Cardiovascular Surgery, 2018).

The study

• Authors: M.C. Ambrogi, P. Bertoglio, V. Aprile, A. Chella, S. Korasidis, G. Fontanini, O. Fanucchi, M. Lucchi, A. Mussi
• Journal: The Journal of Thoracic and Cardiovascular Surgery
• Published: 2018;155(4):1857-1866.e2
• Type of article: Comment
• Cited by: 44 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: The best surgical treatment for malignant pleural mesothelioma is still under a debate, but recent evidence points toward a less-invasive approach to reduce morbidity and mortality. We reported our 10-year experience of a limited surgical approach associated with hyperthermic intrathoracic chemotherapy (HITHOC).

Material And Methods: Between 2005 and 2014, patients with epithelioid or biphasic malignant pleural mesothelioma were treated with lung-diaphragm-pericardium-sparing pleurectomy associated with double-drug HITHOC; at least 3 cycles of adjuvant chemotherapy were then administered. The primary outcome examined was the feasibility of the procedure, whereas secondary outcomes were overall survival and disease-free interval.

Results: Among 49 patients, 41 were male. Median age was 68 years (35-76 years). Histology was epithelioid in 43 cases. Pathologic stage I, II, III, and IV occurred in 12, 14, 20, and 3 cases, respectively. No intraoperative complications or postoperative mortality occurred, whereas morbidity rate was 46.9%. Median hospital stay was 8 days (5-45 days). Actuarial median overall survival was 22 months and a 1-, 2-, and 5-year survival accounted for 79.6%, 45.7%, and 9.9%, respectively. Disease-free survival after surgery was 62%, 37.5%, and 18.5% at 1, 2, and 5 years, respectively. Risk factors analysis for overall survival confirmed a significant role for early stages, epithelioid histology, and fibrinogen serum levels.

Conclusions: Cytoreductive surgery associated with HITHOC and adjuvant chemotherapy appears feasible and safe, with no mortality and low morbidity. Preserving lung and diaphragmatic function might warrant an acceptable long-term outcome.

Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

In plain English

This retrospective study reviewed 49 patients treated in Pisa, Italy, from March 2005 to December 2014 for epithelioid or biphasic malignant pleural mesothelioma. Surgery removed the chest-cavity pleura and larger tumor areas on the lung's surface, sparing the diaphragm and pericardium; 4 patients also had a lung wedge removed. Heated chemotherapy (cisplatin and epirubicin) was circulated in the chest during surgery, followed by at least 3 cycles of cisplatin and pemetrexed. Asbestos exposure was recorded as positive in 23 patients, negative in 7, and uncertain or missing in 19. No patient died within 90 days of surgery (95% confidence interval 0 to 7.2%). Twenty-three of 49 (46.9%; 95% CI 30 to 59%) had complications after surgery, most often anemia. Median overall survival was 22 months (95% CI 13.4 to 30.6), and survival at 1, 2 and 5 years was 79.6%, 45.7% and 9.9%. The disease came back in 39 patients (79.6%), mostly locally. Epithelioid tissue type, early stage and lower blood fibrinogen were associated with longer survival. The authors concluded the approach was feasible and safe, adding that larger, controlled studies are needed.

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 review of medical records of all patients treated with one surgical protocol at a single institution (case series, no comparison group)
• Who was studied: 49 patients (41 male, 8 female; median age 68 years, range 35-76) with epithelioid (43) or biphasic (6) malignant pleural mesothelioma, treated at the University Hospital of Pisa, Italy, March 2005 to December 2014
• Exposure: The study examined a treatment, not an asbestos exposure. Treatment was pleurectomy with partial decortication sparing the diaphragm and pericardium. This was followed by hyperthermic intrathoracic chemotherapy (HITHOC) with cisplatin 80 mg/m2 and epirubicin 25 mg/m2 for 60 minutes, then at least 3 cycles of adjuvant cisplatin and pemetrexed. No fiber types are reported.
• Main results:
  • The operation consisted of complete parietal and mediastinal pleurectomy and removal of the larger lesions on the visceral pleura. The diaphragm and pericardium were always spared.
  • The procedure was pleurectomy and partial decortication. In 4 patients a wedge resection of the lung was also needed.
  • Asbestos exposure among the 49 patients was positive in 23 (46.9%), negative in 7 (14.3%), and uncertain or missing in 19 (38.8%)
  • No intraoperative complications occurred, and the heated chemotherapy perfusion was completed in all patients (in one case it was stopped after 45 minutes for technical problems)
  • No patient showed signs or symptoms of toxicity from the chemotherapy used during surgery
  • Postoperative complications occurred in 23 of 49 patients (46.9%; 95% CI 30-59). The most common was anemia, in 17 patients (34.7%), of whom 13 needed a blood transfusion.
  • No patient died within 90 days after surgery (95% CI 0-7.2)
  • Median hospital stay was 8 days (range 5-45)
  • At a median follow-up of 68.5 months (range 13-127), 14 patients were still alive
  • Median overall survival for the whole group was 22 months. Survival at 1, 2 and 5 years was 79.6%, 45.7% and 9.9%.
  • In Table 5, whose column header gives median overall survival in months with a 95% CI, the current study's median overall survival is 22 months (95% CI 13.4-30.6)
  • Causes of death: 27 patients died after a recurrence. Three died of toxicity from chemotherapy given for recurrence. Five died of causes not related to the disease or treatment.
  • Disease-free interval was 62%, 37.5% and 18.5% at 1, 2 and 5 years. Recurrence occurred in 39 patients (79.6%).
  • Recurrences were mainly local (ipsilateral chest wall, diaphragm or pericardium, drain wounds), in 23 cases. Recurrence was only distant in 4 cases and both local and distant in 8. The site was unknown in 4.
  • In univariate analysis, patients with early-stage disease (stages I and II) had a median overall survival of 35 months, compared with 17 months for stages III and IV (P = .049). Epithelioid patients had a median of 23 months versus 10 months for biphasic patients (P = .022).
  • In multivariate analysis, three factors were associated with better survival: epithelioid histology (HR 0.341; 95% CI 0.120-0.968; P = .043), early stage (HR 0.303; 95% CI 0.123-0.749; P = .010), and low fibrinogen (fibrinogen as a continuous variable, HR 1.007; 95% CI 1.004-1.011; P less than .001). Platelet/lymphocyte and neutrophil/lymphocyte ratios were not significant in this analysis.
• The authors' conclusion: The authors concluded that pleurectomy and focal decortication sparing the diaphragm and pericardium, combined with HITHOC, is a feasible and safe procedure leading to satisfactory long-term results. They added that larger, controlled studies are needed to confirm these outcomes.
• Limitations the authors state:
  • The study was retrospective, and the small cohort and the selection criteria may limit the strength of the conclusions
  • Quality of life and lung function were not objectively assessed after surgery
  • Operative reports did not always clearly define whether resection was R1 or minimal R2
  • Treatments beyond the first 3 chemotherapy cycles, including treatment of recurrence, varied with each referring oncologist's preference

Topics

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

Medical terms in this study, explained in our Lexicon: Diaphragm, Chemotherapy, Pleural Mesothelioma, Intrathoracic, Epithelioid, Biphasic Mesothelioma, Pericardium, Overall Survival.

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• Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine, prophylactic radiotherapy, and systemic chemotherapy in patients with malignant pleural mesothelioma: a 10-year experience — L. Lang-Lazdunski, A. Bille, et al. (2015)
• Cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion for malignant pleural tumours: perioperative management and clinical experience — M. Ried, T. Potzger, et al. (2013)
• Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin in pediatric patients with peritoneal mesothelioma: a single institution experience and long term follow up — P. Malekzadeh, M. Good, et al. (2021)
• Outcomes of Cytoreductive Surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients older than 70 years; survival benefit at considerable morbidity and mortality — K.I. Votanopoulos, N.A. Newman, et al. (2013)
• Cytoreductive surgery and hyperthermic intrapleural chemotherapy for malignant pleural diseases: preliminary experience — M. Migliore, D. Calvo, et al. (2015)

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