Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) for the treatment of malignant mesothelioma

Our plain-English summary of Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) for the treatment of malignant mesothelioma, by U. Giger-Pabst, C. Demtröder, T.A. Falkenstein, et al (BMC Cancer, 2018).

The study

• Authors: U. Giger-Pabst, C. Demtröder, T.A. Falkenstein, M. Ouaissi, T.O. Götze, G.A. Rezniczek, C.B. Tempfer
• Journal: BMC Cancer
• Published: 2018;18(1):442
• Cited by: 57 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Patients with recurrent malignant epithelioid mesothelioma (MM) after surgery and standard chemotherapy with cisplatin and pemetrexed have limited treatment options.

Methods: We performed a retrospective cohort study of patients with recurrent MM undergoing Pressurized IntraPeritoneal/Thoracal Aerosol Chemotherapy (PIPAC/PITAC) with doxorubicin 1.5 mg/m2 and cisplatin 7.5 mg/m2. Data were retrospectively collected in a prospective registry of patients undergoing PIPAC/PITAC. Study outcomes were microscopic tumor regression grade (TRG), survival and adverse events (v4.0 CTCAE).

Results: A total of 29 patients (m/f = 17/12) with MM with a mean age of 62.4 (range: 42 to 84) years were analyzed. A total of 74 PIPAC and 5 PITAC procedures were performed. The mean number of PIPAC applications was 2.5 (range: 0 to 10) per patient. Twenty patients (69%) had > 2 PIPAC procedure and were eligible for TRG analysis. TRG 1 to 4 was observed in 75% (15/20) of patients. Major regression (TRG 3) or complete regression (TRG 4) was observed in 20% and 10%, respectively. PIPAC induced significant tumor regression in 51.7% (15/29) of patients with a cumulative effect after repetitive PIPACs (PIPAC #1 vs. PIPAC #2: p = 0.001; PIPAC #1 vs. PIPAC #3: p = 0.001; PIPAC #1 vs. PIPAC #4: p = 0.001). Postoperative CTCAE grade 4 complications were observed in two patients (6.9%) who had cytoreductive surgery (CC2) and intraoperative PIPAC. One patient (3.4%) died due to postoperative kidney insufficiency. After a follow up of 14.4 (95% CI: 8.1 to 20.7) months after the last PIPAC/PITAC application, median overall survival was 26.6 (95% CI: 9.5 to 43.7) months (from the first application).

Conclusion: After prior abdominal surgery and systemic chemotherapy, repetitive PIPAC applications are feasible and safe for patients with end-stage MM. Furthermore, PIPAC induces significant histological regression of malignant mesothelioma in the majority of patients. PITAC is feasible, but its safety and efficacy to control malignant pleural effusion remain unclear.

In plain English

This retrospective cohort study used registry data from Marien Hospital Herne, Germany, on 29 patients (17 men, 12 women) with epithelioid malignant mesothelioma in the peritoneum, included June 2012 to October 2017. Most had prior surgery or systemic chemotherapy. Twenty-five received at least one treatment of doxorubicin and cisplatin sprayed as a pressurized aerosol into the abdomen (PIPAC), mostly during keyhole surgery; four received none. Three also received it in the chest (PITAC). Of 20 patients assessable after two or more cycles, 15 showed microscopic tumor regression, major in 4 and complete in 2. Of all 29, regression was seen in 15 (51.7%). Among the 25 treated, median overall survival from first treatment was 26.6 months (95% CI 9.5 to 43.7). There were 34 postoperative complications across 79 procedures; two patients who also had partial tumor-removal surgery developed serious bowel leaks, and one other patient died of kidney failure. The authors concluded repeated PIPAC was feasible and safe, noting the small sample, retrospective design and possible patient selection. The article reported no patient asbestos exposure, mentioning asbestos only when citing other studies.

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 cohort study (case series) using data from a prospective PIPAC/PITAC registry at a single center
• Who was studied: 29 patients (17 male, 12 female; mean age 62.4 years, range 42 to 84) with epithelioid malignant mesothelioma with peritoneal involvement, included June 2012 to October 2017 at Marien Hospital Herne, Ruhr-Universität Bochum, Germany. 5 were initially diagnosed with malignant pleural mesothelioma that later spread into the peritoneal cavity, and most had prior surgery and/or systemic chemotherapy. Of the 29, 25 received at least one PIPAC cycle and 4 received none.
• Exposure: The study examined treatment, not asbestos exposure. Patients received pressurized aerosol chemotherapy into the abdomen (PIPAC), and 3 patients also received it into the chest (PITAC). Each treatment used doxorubicin 1.5 mg/m2 followed by cisplatin 7.5 mg/m2, and at least three cycles six weeks apart were intended. Of 79 successful procedures, 71 were laparoscopic PIPAC, 3 were PIPAC with open laparotomy, and 5 were PITAC. Asbestos exposure of the patients was not reported.
• Main results:
  • Of the 29 included patients, 25 successfully received a first PIPAC cycle.
  • Among 20 patients eligible for tumor regression grading (two or more PIPAC cycles), 75% (15/20) showed objective histological tumor regression. Major regression (TRG 3) was seen in 20% (4/20) and complete regression (TRG 4) in 10% (2/20).
  • On an intention-to-treat basis (all 29 patients), histological tumor regression was found in 51.7% (15/29).
  • In biopsies taken before the first PIPAC, 19 of 25 patients (76%) had no tumor regression (TRG 0) and 6 of 25 (24%) had minimal regression (TRG 1). All 6 had previous systemic chemotherapy.
  • Regression grades rose significantly after the first PIPAC (PIPAC #1 vs #2, #3 and #4: each p less than 0.0001), with no further significant increase in later cycles.
  • In 25 patients who received at least one PIPAC cycle, median overall survival from the first application was 26.6 months (95% CI: 9.5 to 43.7). Median follow-up was 14.4 months (95% CI: 8.1 to 20.7), and ten patients had died by the end of the study period.
  • There were 34 postoperative complications (CTCAE grade 1 to 4) across 79 PIPAC/PITAC procedures, reported as an overall morbidity rate of 43.0% (34/79).
  • Two patients who had subtotal cytoreductive surgery (CC2) with simultaneous PIPAC had grade 4 complications (small bowel anastomotic leakage). Both recovered.
  • One patient died after the second PIPAC cycle due to kidney insufficiency. The procedure-related mortality rate was 1.3% (1/79).
  • Minimally invasive access to the abdomen failed at the first attempt in 7 of 29 patients, a primary non-access rate of 24.1%.
  • Malignant ascites volume did not change significantly over repeated PIPAC cycles (p greater than 0.99 in the supplementary figure; p = 0.99 in the main text).
  • The authors reported a notable increase in quality-of-life functional scales during PIPAC treatment. No statistical test was reported for this.
  • In the 3 patients who also received PITAC (5 procedures), no perioperative complications occurred.
• The authors' conclusion: The authors concluded that repetitive PIPAC was feasible and safe in patients with end-stage peritoneal mesothelioma after prior major abdominal surgery and systemic chemotherapy. They also concluded that peritoneal mesothelioma was highly sensitive to PIPAC, and that PITAC was feasible but its safety and efficacy for malignant pleural effusion remained unclear.
• Limitations the authors state:
  • Small sample size.
  • The retrospective design limits generalizability.
  • Patient selection and self-selection may have favored PIPAC.
  • It is unclear whether the observed survival is due to PIPAC or to selection bias.

Topics

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

Medical terms in this study, explained in our Lexicon: Chemotherapy, Mesothelioma, Epithelioid, Cisplatin, Pemetrexed (Alimta), Cohort Study, Doxorubicin, Cytoreductive Surgery.

Related studies

• Quality of life of patients with end-stage peritoneal metastasis treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) — K. Odendahl, W. Solass, et al. (2015)
• Multicenter comprehensive methodological and technical analysis of 832 pressurized intraperitoneal aerosol chemotherapy (PIPAC) interventions performed in 349 patients for peritoneal carcinomatosis treatment: An international survey study — M. Nowacki, M. Alyami, et al. (2018)
• Unresectable peritoneal metastasis treated by pressurized intraperitoneal aerosol chemotherapy (PIPAC) leading to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy — M. Alyami, F. Mercier, et al. (2021)
• Oxaliplatin use in pressurized intraperitoneal aerosol chemotherapy (PIPAC) is safe and effective: A multicenter study — O. Sgarbura, M. Hübner, et al. (2019)
• Multicentric initial experience with the use of the pressurized intraperitoneal aerosol chemotherapy (PIPAC) in the management of unresectable peritoneal carcinomatosis — M. Alyami, J. Gagniere, et al. (2017)
• Neoadjuvant Pressurized Intraperitoneal Aerosol Chemotherapy for Conversion to Cytoreductive Surgery in Unresectable Malignant Peritoneal Mesothelioma: A Report of 2 Cases — A. Urbano-Ruiz, B. Latronico Palma, et al. (2026)

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