Patterns of failure after trimodality therapy for malignant pleural mesothelioma

Our plain-English summary of Patterns of failure after trimodality therapy for malignant pleural mesothelioma, by E.H. Baldini, A. Recht, G.M. Strauss, et al (The Annals of Thoracic Surgery, 1997).

The study

• Authors: E.H. Baldini, A. Recht, G.M. Strauss, M.M. DeCamp, S.J. Swanson, M.J. Liptay, S.J. Mentzer, D.J. Sugarbaker
• Journal: The Annals of Thoracic Surgery
• Published: 1997;63(2):334-8
• Cited by: 229 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Malignant pleural mesothelioma is uncommon, and presently, no standard treatment of this disease exists. The objective of our analysis was to study the patterns of failure for malignant pleural mesothelioma after trimodality treatment consisting of extrapleural pneumonectomy, chemotherapy, and radiation therapy.

Methods: Between 1987 and 1993, 49 patients with malignant pleural mesothelioma underwent extrapleural pneumonectomy. There were two perioperative deaths, and 1 patient died 5 weeks after extrapleural pneumonectomy. Thirty-five of the surviving patients received adjuvant chemotherapy (32/35 received cyclophosphamide, doxorubicin, and cisplatin) followed by hemithorax radiation therapy. Ten patients received chemotherapy but no radiation therapy, and 1 patient received no adjuvant therapy. Median follow-up time for the 23 living patients from the date of operation was 18 months.

Results: Of the 46 evaluable patients, 25 had recurrence (54%), with a median time to first failure of 19 months (range, 5 to 51 months). The sites of first recurrence were local in 35% of patients, abdominal in 26%, the contralateral thorax in 17%, and other distant sites in 8%. (Some patients had recurrence in multiple sites simultaneously.)

Conclusions: The most common site of failure after trimodality therapy was the ipsilateral hemithorax. Isolated distant failures were uncommon. Future strategies should investigate methods of enhancing local tumor control.

In plain English

This Boston study examined where malignant pleural mesothelioma recurred after surgery (extrapleural pneumonectomy), chemotherapy and radiation. The authors called it a phase II trial. Between January 1987 and June 1993, 49 patients had the surgery. Of these, 46 were evaluable; 35 received all three treatments. The article does not report the patients' asbestos exposure. Of the 46, 25 (54%) recurred, at a median of 19 months. Among 24 patients with evaluable recurrence sites, the most common first site was the chest on the original tumor's side: 16 (67%). The abdomen was involved in 12, the opposite chest in 8 and the central nervous system in 2; some had several sites. Median survival for all 49 patients was 22 months, and estimated 3-year survival was 34%, plus or minus 17%. Local recurrence as the first site of failure occurred in 11 of 35 patients (31%) given radiation and 5 of 11 (45%) not given it, a difference that was not statistically significant. The authors concluded that failure was mainly local and that future strategies should try to improve local control.

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: Phase II trial (single-institution treatment series) analysing patterns of recurrence; data abstracted from clinical records
• Who was studied: 49 patients with malignant pleural mesothelioma confined to one side of the chest (Butchart stage I) who underwent extrapleural pneumonectomy at Brigham and Women's Hospital, Boston, between January 1987 and June 1993. There were 37 men and 12 women, with a median age of 55 years. 46 patients were evaluable for recurrence.
• Exposure: This was not an asbestos-exposure study, and asbestos exposure is not reported. The treatment studied was extrapleural pneumonectomy followed by chemotherapy (mostly cyclophosphamide, doxorubicin and cisplatin) and radiation to the hemithorax. Of the 46 patients who survived surgery, 35 received all three treatments, 10 received surgery and chemotherapy only, and 1 received no further treatment.
• Main results:
  • 25 of the 46 evaluable patients (54%) had a recurrence; the median time to first recurrence was 19 months
  • Among the 24 patients with evaluable recurrence (Table 1), the ipsilateral hemithorax (same side of the chest) was the most common site of first failure: 16 patients, 67% of recurrences, 35% of all patients
  • Other sites of first recurrence: abdomen in 12 patients (26% of all patients, 50% of recurrences); contralateral hemithorax in 8 (17%, 33%); distant sites in 2 (4%, 8%). Some patients had recurrence in multiple sites at once.
  • Recurrence in the ipsilateral hemithorax only occurred in 6 patients (13% of all patients, 25% of recurrences)
  • Both distant recurrences involved the central nervous system
  • Median survival for all 49 patients was 22 months. The 3-year actuarial survival rate was 34% plus or minus 17%, and the 3-year rate of freedom from disease progression was 33% plus or minus 18%.
  • 21 of the 25 patients who had a recurrence had died, with a median of 3 months from relapse to death
  • Local recurrence as the first site of failure (any local component, Table 3) occurred in 11 of 35 patients (31%) who received radiation versus 5 of 11 (45%) who did not (p = 0.62)
  • Among patients with positive resection margins, local recurrence as the first site of failure was lower with radiation (6 of 23, 26%) than without (3 of 5, 60%); all p values in this analysis were not significant
  • Median time to relapse was 20 months for the 35 patients who received all three treatments and 11 months for the 11 who did not, but there was no difference in median survival between these groups
  • There were two perioperative deaths among the 49 patients (4%); one further patient died 5 weeks after surgery of an unknown cause
• The authors' conclusion: The authors concluded that selected patients can obtain up to a 34% 3-year survival rate after this treatment, that the predominant pattern of failure is local, and that future treatment strategies should attempt to improve local control
• Limitations the authors state:
  • The trial could not separate the contribution of any single treatment (surgery, chemotherapy or radiation) to outcome
  • Comparing patients who did and did not receive radiation is subject to potential biases
  • Comparisons of outcomes with other published series may be biased

Topics

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

Medical terms in this study, explained in our Lexicon: Trimodality Therapy, Pleural Mesothelioma, Extrapleural Pneumonectomy (EPP), Chemotherapy, Doxorubicin, Cisplatin, Hemithorax, Adjuvant Therapy.

Related studies

• Updated patterns of failure after multimodality therapy for malignant pleural mesothelioma — E.H. Baldini, W.G. Richards, et al. (2015)
• Patterns of failure, toxicity, and survival after extrapleural pneumonectomy and hemithoracic intensity-modulated radiation therapy for malignant pleural mesothelioma — D.R. Gomez, D.S. Hong, 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)
• Improved Outcomes with Modern Lung-Sparing Trimodality Therapy in Patients with Malignant Pleural Mesothelioma — F. Shaikh, M.G. Zauderer, et al. (2017)
• 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)
• Heterologous sarcomatoid pleural mesothelioma with osteosarcomatous differentiation: a report of autopsy case that accomplished trimodality therapy and review of the literature — H. Itano, T. Takeda, et al. (2020)

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