Current Management and Future Opportunities for Peritoneal Metastases: Peritoneal Mesothelioma

Our plain-English summary of Current Management and Future Opportunities for Peritoneal Metastases: Peritoneal Mesothelioma, by H.R. Alexander, C.Y. Li, T.J. Kennedy (Annals of Surgical Oncology, 2018).

The study

• Authors: H.R. Alexander, C.Y. Li, T.J. Kennedy
• Journal: Annals of Surgical Oncology
• Published: 2018;25(8):2159-2164
• Type of article: Review
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: Diffuse malignant peritoneal mesothelioma (MPM) is a rare and ultimately fatal cancer that was first described just over a century ago. It is a diffuse malignancy arising from the mesothelial lining of the peritoneum; morbidity and mortality from MPM is due to its propensity to progress locoregionally within the abdominal cavity.

Methods: The purpose of this article is to review the current state-of-the-science related to the diagnosis, staging, and treatment of MPM.

Results: The condition afflicts men and women equally and the peak incidence is between 55 and 60 years of age although it can arise in the young and elderly. Patients afflicted with MPM most commonly present with nonspecific abdominal symptoms that usually lead to diagnosis when the condition is relatively advanced. Historically, median overall survival for MPM patients without treatment is < 1 year. The couplet of systemic pemetrexed and cisplatin has an overall response rate of approximately 25% and a median overall survival of approximately 1 year.

Conclusion: The available data, almost all retrospective in nature, have shown that in selected patients, operative cytoreduction (CRS) and regional chemotherapy administered as hyperthermic intraoperative peritoneal chemotherapy (HIPEC) or early postoperative intraperitoneal chemotherapy (EPIC) is associated with long-term survival. Studies on the molecular biology of MPM have yielded new insights relating to the potentially important role of the phosphoinsitide-3-kinase/mammalian target of rapamycin (PI3 K/mTOR) pathways and immune checkpoint inhibitors that may translate into new therapeutic options for patients with diffuse MPM.

In plain English

This article is a review, not a new study. The authors summarized published research on the diagnosis, staging and treatment of diffuse malignant peritoneal mesothelioma (MPM), a cancer of the lining of the abdomen. The article does not discuss asbestos. In the studies reviewed, median overall survival was 6 months in treatment-naive patients, compared with 34 to 92 months in selected patients who underwent an operation. The largest multicenter study reviewed, of 405 patients at 29 centers in the US and Europe, reported a median survival of 53 months and a 5-year survival of 47%. Factors linked with shorter survival included age over 60, male sex, high-grade tumor type, incomplete surgery and high platelet counts before treatment. In a program that treated over 1000 patients with pleural or peritoneal mesothelioma, the drugs pemetrexed and cisplatin produced a 26% response rate, and overall survival was approximately 13 months. The authors concluded that cytoreductive surgery (CRS) with heated chemotherapy given inside the abdomen (HIPEC) has become widely acknowledged as the preferred first-line treatment in selected patients. They noted that the available data are almost all retrospective.

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: Review of published studies on the diagnosis, staging and treatment of malignant peritoneal mesothelioma
• Who was studied: No single study population. The review draws on published studies of patients with diffuse malignant peritoneal mesothelioma, including single-center reviews, two large multicenter reviews, a meta-analysis, and an analysis of 1591 patients in the US SEER database diagnosed between 1973 and 2006
• Exposure: Not an exposure study, and asbestos is not discussed. The treatments reviewed were cytoreductive surgery with regional chemotherapy given as HIPEC or as early postoperative intraperitoneal chemotherapy (EPIC), and systemic pemetrexed with cisplatin
• Main results:
  • In the studies reviewed, median overall survival was 6 months in treatment-naive patients, compared with 34 to 92 months in selected patients undergoing an operation
  • In the largest multicenter retrospective study reviewed (405 patients, 29 centers, US and Europe), actuarial median overall survival was 53 months and 5-year overall survival was 47%
  • In a three-center US review of 211 MPM patients, actuarial median overall survival was 38 months and 5-year overall survival was 41%
  • A meta-analysis of 20 publications covering over 1000 MPM patients treated with operative CRS reported a 5-year overall survival of 42%
  • Under a proposed staging system, patients with T1 N0 M0 disease (stage I) had a 5-year survival of 87%; stage II was 53% and stage III was 29%
  • In an institutional analysis of 100 patients who had CRS and HIPEC, median survival was 13 months in patients with preoperative thrombocytosis (high platelet count) and 58 months in those with normal platelet counts
  • Studies reviewed linked age over 60 years, male sex, biphasic or sarcomatoid histology, deep tissue invasion, solid tumor masses on the small bowel or its mesentery, and pretreatment thrombocytosis with a lower chance of complete cytoreduction and with shortened survival
  • In 65 patients who had CRS and HIPEC at a high-volume center, major postoperative complications (grade III/IV) occurred in 23 patients (35%), and the 60-day mortality rate was 6%
  • In the US Expanded Access Program (over 1000 patients with pleural or peritoneal mesothelioma), pemetrexed plus cisplatin gave an overall response rate of 26% and a stable disease rate of 45%. Overall survival with chemotherapy alone was approximately 13 months
  • Two large retrospective studies reviewed did not show a benefit from systemic chemotherapy given before or after CRS and HIPEC
• The authors' conclusion: The authors concluded that CRS and HIPEC has become widely acknowledged as the preferred first-line treatment for selected patients with MPM. They also concluded that careful patient selection and expertise are essential, and that drugs targeting the mTOR or PI3K pathways and checkpoint inhibitors may become useful
• Limitations the authors state:
  • The authors note that the available evidence on surgical treatment is almost all retrospective
  • The authors state that the optimal intraperitoneal chemotherapy regimen after CRS has not been defined
  • The authors state that the benefit of systemic chemotherapy before or after CRS and HIPEC has not been established

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, Peritoneum, Staging, Median Overall Survival, Pemetrexed (Alimta), Cisplatin, Cytoreductive Surgery, Chemotherapy.

Related studies

• Current trends in the management of malignant peritoneal mesothelioma — J.T. Miura, F.M. Johnston, et al. (2014)
• Association between hospital finances, payer mix, and complications after hyperthermic intraperitoneal chemotherapy: deficiencies in the current healthcare reimbursement system and future implications — M.H. Squires, C.A. Staley, et al. (2015)
• Lymph node metastases in diffuse malignant peritoneal mesothelioma — D. Baratti, S. Kusamura, et al. (2010)
• Surgical biology for the clinician: peritoneal mesothelioma: current understanding and management — T.C. Chua, T.D. Yan, et al. (2009)
• Role of hyperthermic intraoperative peritoneal chemotherapy in the management of peritoneal metastases — D. Elias, D. Goéré, et al. (2014)
• Peritoneal metastases from small bowel cancer: Results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in The Netherlands — T.R. van Oudheusden, V.E. Lemmens, et al. (2015)

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