Malignant peritoneal mesothelioma: prognostic factors and oncologic outcome analysis

Our plain-English summary of Malignant peritoneal mesothelioma: prognostic factors and oncologic outcome analysis, by D. Magge, M.S. Zenati, F. Austin, et al (Annals of Surgical Oncology, 2014).

The study

• Authors: D. Magge, M.S. Zenati, F. Austin, A. Mavanur, M. Sathaiah, L. Ramalingam, H. Jones, A.H. Zureikat, M. Holtzman, S. Ahrendt, J. Pingpank, H.J. Zeh, D.L. Bartlett, H.A. Choudry
• Journal: Annals of Surgical Oncology
• Published: 2014;21(4):1159-65
• Cited by: 84 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Most patients with malignant peritoneal mesothelioma (MPM) present with late-stage, unresectable disease that responds poorly to systemic chemotherapy while, at the same time, effective targeted therapies are lacking. We assessed the efficacy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) in MPM.

Methods: We prospectively analyzed 65 patients with MPM undergoing CRS/HIPEC between 2001 and 2010. Kaplan-Meier survival curves and multivariate Cox-regression models identified prognostic factors affecting oncologic outcomes.

Results: Adequate CRS was achieved in 56 patients (CC-0 = 35; CC-1 = 21), and median simplified peritoneal cancer index (SPCI) was 12. Pathologic assessment revealed predominantly epithelioid histology (81 %) and biphasic histology (8 %), while lymph node involvement was uncommon (8 %). Major postoperative morbidity (grade III/IV) occurred in 23 patients (35 %), and 60-day mortality rate was 6 %. With median follow-up of 37 months, median overall survival was 46.2 months, with 1-, 2-, and 5-year overall survival probability of 77, 57, and 39 %, respectively. Median progression-free survival was 13.9 months, with 1-, 2-, and 5-year disease failure probability of 47, 68, and 83 %, respectively. In a multivariate Cox-regression model, age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), aggressive histology (epithelioid, biphasic), and postoperative sepsis were joint significant predictors of poor survival (chi square = 42.8; p = 0.00001), while age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), and aggressive histology (epithelioid, biphasic) were joint significant predictors of disease progression (Chi square = 30.6; p = 0.00001).

Conclusions: Tumor histology, disease burden, and the ability to achieve adequate surgical cytoreduction are essential prognostic factors in MPM patients undergoing CRS/HIPEC.

In plain English

This study examined 65 consecutive patients with malignant peritoneal mesothelioma (cancer of the abdominal lining) treated at the University of Pittsburgh between March 2001 and August 2010, using data recorded as treatment happened. All had cytoreductive surgery (removal of visible tumor) followed by heated chemotherapy circulated through the abdomen (HIPEC). Asbestos exposure was documented in 18 of the 47 patients with this information (38%). All or nearly all visible tumor was removed in 56 patients (86%). Major complications occurred in 23 patients (35%), and 4 patients (6%) died within 60 days. Median overall survival was 46.2 months, with an estimated 39% alive at 5 years. Median progression-free survival was 13.9 months. In the combined analysis, older age, a tumor burden score above 15, incomplete tumor removal, and sarcomatoid or biphasic tumor type were linked to shorter survival and earlier progression. The authors also named postoperative sepsis as a survival predictor, although their table gives it p = 0.08. Asbestos exposure showed a trend toward poorer survival (p = 0.06) that was not statistically significant. The authors concluded that tumor type, disease burden and adequate tumor removal are essential prognostic factors.

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: Single-institution analysis of consecutive patients drawn from a prospectively maintained database (case series of treated patients), with Kaplan-Meier survival estimates and Cox regression
• Who was studied: 65 patients with malignant peritoneal mesothelioma treated at the University of Pittsburgh, March 2001 to August 2010. Disease was confined to the peritoneal cavity in 56 patients (86%), and 9 patients (14%) had both peritoneal and pleural disease. Mean age was 54 years, and 74% were male.
• Exposure: The study is about treatment, not asbestos dose. The treatment studied was cytoreductive surgery plus HIPEC, mostly with mitomycin C (94%). A history of asbestos exposure was documented in 18 of 47 patients with data (38.3%). No fiber types are given.
• Main results:
  • Adequate cytoreduction (CC-0/1) was achieved in 86% of patients (CC-0 in 35, CC-1 in 21). The median simplified peritoneal cancer index was 12.
  • Among all 65 patients, major postoperative complications (grade III/IV) occurred in 23 patients (35%). The 60-day mortality was 6% (four patients).
  • Median follow-up was 36.8 months. Median overall survival was 46.2 months, with 1-, 2- and 5-year overall survival probabilities of 77, 57 and 39%. Median progression-free survival was 13.9 months.
  • In the multivariate model for mortality, the authors identified these predictors:
• age at surgery (HR 1.1, 95% CI 1.02–1.1)
• SPCI above 15 (HR 2.6, 1.1–6.2)
• incomplete cytoreduction CC-2/3 (HR 2.6, 1.0–6.9)
• sarcomatoid or biphasic histology (HR 5.5, 1.9–16.1)
• postoperative sepsis (HR 2.1, 0.9–4.9, p = 0.08)

The authors called these joint significant predictors of poor survival (chi square = 42.8; p = 0.00001).

• In the multivariate model for disease progression, the authors identified these joint significant predictors (chi square = 30.6; p = 0.00001):
• age at surgery (HR 1.03)
• SPCI above 15 (HR 3.4, 95% CI 1.5–7.3)
• incomplete cytoreduction (HR 6.4, 1.5–26.3)
• sarcomatoid or biphasic histology (HR 5.4, 2.1–14.0)
  • Median survival was 51.5 months (95% CI 23–90.2) for epithelioid, well-differentiated papillary or multicystic tumors. It was 10.5 months (95% CI 0.5–17) for sarcomatoid or biphasic tumors.
  • Patients with asbestos exposure showed a trend toward poorer survival on univariate analysis (p = 0.06). This did not reach the study's significance threshold.
• The authors' conclusion: The authors concluded the following:
• Tumor histology, disease burden and the ability to achieve adequate cytoreduction are essential prognostic factors.
• CRS/HIPEC is effective in select patients.
• Patients with sarcomatoid or biphasic histology, high tumor burden, or tumors that cannot be adequately cytoreduced are poor candidates.
• Careful patient selection is essential.

Topics

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

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Unresectable, Chemotherapy, Cytoreductive Surgery, HIPEC, Peritoneal Cancer Index (PCI), Epithelioid, Histology.

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• Impact of Combination Chemotherapy in Peritoneal Mesothelioma Hyperthermic Intraperitoneal Chemotherapy (HIPEC): The RENAPE Study — B. Malgras, E. Gayat, et al. (2018)
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