Outcomes of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma and predictors of survival

Our plain-English summary of Outcomes of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma and predictors of survival, by S.N.S. Gilani, A. Mehta, A. Garcia-Fadrique, et al (International Journal of Hyperthermia, 2018).

The study

• Authors: S.N.S. Gilani, A. Mehta, A. Garcia-Fadrique, B. Rowaiye, V. Jenei, S. Dayal, K. Chandrakumaran, N. Carr, F. Mohamed, T. Cecil, B. Moran
• Journal: International Journal of Hyperthermia
• Published: 2018;34(5):578-584
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) benefits selected patients with peritoneal mesothelioma. We present the outcomes of this treatment strategy in a UK peritoneal malignancy national referral centre.

Methods: Observational retrospective analysis of data prospectively collected in a dedicated peritoneal malignancy database between March 1998 and January 2016.

Results: Of 1586 patients treated for peritoneal malignancy, 76 (4.8%) underwent surgery for peritoneal mesothelioma. Median age was 49 years (range 21-73 years). 34 patients (45%) were female. Of the 76 patients, 39 (51%) had low grade histological subtypes (mostly multicystic mesothelioma), and 37 (49%) had diffuse malignant peritoneal mesothelioma (DMPM; mostly epithelioid mesothelioma). Complete cytoreduction was achieved in 52 patients (68%) and maximal tumour debulking (MTD) was performed in 20 patients (26%); the remaining 4 patients (5%) underwent a laparotomy with biopsy only. HIPEC was administered in 67 patients (88%). Median overall (OS) and disease-free survival (DFS) after CRS was 97.8 (80.2-115.4) and 58.8 (47.4-70.3) months, respectively. After complete cytoreduction, 100% overall survival was observed amongst patients with low-grade disease. Ki-67 proliferation index was significantly associated with survival outcomes after complete cytoreduction for DMPM and was an independent predictor of decreased survival.

Conclusion: With adequate patient selection (guided by histological classification and Ki-67 proliferation index) and complete cytoreduction with HIPEC, satisfactory outcomes can be achieved in selected patients with peritoneal mesothelioma.

In plain English

This study reviewed patients operated on for peritoneal mesothelioma at a UK referral centre, 1998 to 2016. Of 1586 patients treated for peritoneal malignancy, 76 had peritoneal mesothelioma: 39 low-grade (mostly multicystic) and 37 diffuse malignant peritoneal mesothelioma (DMPM). Treatment was surgery, with heated abdominal chemotherapy (HIPEC) for most. Asbestos exposure was not examined. Complete cytoreduction (no tumour left, or only nodules up to 2.5 mm) was achieved in 52 patients (68%): 49% with DMPM and 87% with low-grade disease. Overall median survival was 97.8 months (95% CI 80.2 to 115.4). Every low-grade patient with complete cytoreduction was alive at the end of follow-up. In DMPM patients with complete cytoreduction, a Ki-67 index (the percentage of tumour cells staining for a marker of cell proliferation) of 7% or higher was linked to significantly shorter survival. Ki-67 independently predicted decreased survival (hazard ratio 3.4, 95% CI 1.7 to 18.1). Five patients (7%) had serious complications. The authors concluded that satisfactory outcomes can be achieved in selected patients when selection is guided by histology and Ki-67 and complete cytoreduction with HIPEC is achieved. They noted their study was relatively small.

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: Observational retrospective analysis of data prospectively collected in a single centre's peritoneal malignancy database (surgical case series)
• Who was studied: 76 patients who underwent surgery for peritoneal mesothelioma, out of 1586 patients treated for peritoneal malignancy at a UK peritoneal malignancy national referral centre (Basingstoke), March 1998 to January 2016. 39 had low-grade peritoneal mesothelioma (mostly multicystic) and 37 had diffuse malignant peritoneal mesothelioma (mostly epithelioid). Median age was 49 years, and 34 were female.
• Exposure: The study did not assess asbestos exposure. The treatment studied was cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). HIPEC was given to 67 patients: 57 received cisplatin and doxorubicin, and 10 received mitomycin C.
• Main results:
  • Complete cytoreduction was defined as CC0 (no residual disease) or CC1 (residual nodules up to 2.5 mm).
  • Of all 76 patients, complete cytoreduction was achieved in 52 (68%), maximal tumour debulking was performed in 20 (26%), and 4 (5%) had biopsy only. Of the 52, CC0 was achieved in 37 and CC1 in 15.
  • Complete cytoreduction was less common in DMPM patients (18 patients; 49%) than in low-grade patients (34 patients; 87%).
  • For the entire study population, median overall survival was 97.8 months (95% CI 80.2 to 115.4). The 3- and 5-year overall survival rates were 75.8% and 67.7%.
  • For the entire study population, median disease-free survival was 58.8 months (95% CI 47.4 to 70.3). The 3- and 5-year disease-free survival rates were 67.5% and 60.4%.
  • After complete cytoreduction (all subtypes), median overall survival was 127.0 months (95% CI 111.0 to 143.0). The 3- and 5-year survival rates were 87.6% and 79.7%.
  • After maximal tumour debulking, median overall survival was 43.2 months (95% CI 20.0 to 66.4). The 3- and 5-year survival rates were 45.0% and 36.1%.
  • All patients with low-grade disease who had complete cytoreduction were alive at the end of follow-up. Among DMPM patients with complete cytoreduction, mean overall survival was 45.7 months (95% CI 28.2 to 63.2), with 3- and 5-year survival of 62.5% and 37.5%.
  • Ki-67 was measured as the percentage of tumour cells with positive nuclear staining. Among DMPM patients with complete cytoreduction, mean overall survival was 70.0 months (95% CI 47.5 to 92.0) with a Ki-67 index below 7%, and 32.8 months (95% CI 15.0 to 50.0) with a Ki-67 index of 7% or higher.
  • In DMPM patients after complete cytoreduction, the Peritoneal Cancer Index (extent of disease) had no significant association with survival.
  • In multivariate analysis of DMPM patients after complete cytoreduction, the Ki-67 proliferation index was an independent predictor of decreased overall survival (HR 3.4; 95% CI 1.7 to 18.1; p = 0.040).
  • There was no 30-day postoperative mortality. Death within 90 days occurred in 2 of 76 patients (2.6%), and 5 patients (7%) developed Clavien-Dindo grade III/IV complications.
• The authors' conclusion: The authors concluded that, with adequate patient selection (guided by histological classification and Ki-67 proliferation index) and complete cytoreduction with HIPEC, satisfactory outcomes can be achieved in selected patients with peritoneal mesothelioma.
• Limitations the authors state:
  • The relatively small study population may have limited the ability to detect an association between the Peritoneal Cancer Index and survival.
  • The case mix reflects the unit's referral pattern: a relatively high proportion of low-grade lesions and no sarcomatoid mesothelioma.

Topics

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

Medical terms in this study, explained in our Lexicon: Cytoreductive Surgery, HIPEC, Peritoneal Mesothelioma, Histological Subtype, Multicystic Mesothelioma (MCM), Epithelioid, Mesothelioma, Laparotomy.

Related studies

• Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent or progressive diffuse malignant peritoneal mesothelioma: clinicopathologic characteristics and survival outcome — C. Ihemelandu, L. Bijelic, et al. (2015)
• Radiological predictors of complete cytoreduction in 59 patients with peritoneal mesothelioma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy at a UK referral centre — A. Chandramohan, A. Thrower, et al. (2017)
• The results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in 1200 patients with peritoneal malignancy — B. Moran, T. Cecil, et al. (2015)
• Is Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy Justified for Biphasic Variants of Peritoneal Mesothelioma? Outcomes from the Peritoneal Surface Oncology Group International Registry — K.I. Votanopoulos, P. Sugarbaker, et al. (2018)
• Overall survival of pseudomyxoma peritonei and peritoneal mesothelioma patients after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy can be predicted by computed tomography quantified sarcopenia — A. Galan, P. Rousset, et al. (2018)
• The Role of Ki-67 and Pre-cytoreduction Parameters in Selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) Patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — S. Kusamura, P.A. Torres Mesa, et al. (2016)

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