Multicentric initial experience with the use of the pressurized intraperitoneal aerosol chemotherapy (PIPAC) in the management of unresectable peritoneal carcinomatosis

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Abstract

Background

PIPAC is a recent approach for intraperitoneal chemotherapy with promising results for patients with peritoneal carcinomatosis (PC). We aimed to evaluate the postoperative outcome of PIPAC in patients with non-resectable PC during our initial experience of the technique.

Methods

All patients who underwent PIPAC for non-resectable PC in three centers were analyzed regarding postoperative outcomes.

Results

Seventy-three patients underwent 164 PIPAC. PC was from colorectal, gastric, ovarian, malignant mesothelioma, pseudomyxoma peritonei or other origins in 20, 26, 13, 8, 1 and 5 patients respectively. Forty-five (62%), 31 (42%), 8 (11%), 6 (8%), 1 (1%) patients underwent a second, third, fourth, fifth, and sixth PIPAC respectively. At the time of the first PIPAC, the median PCI was 17 (1–39), 57 patients presented with symptomatic PC (pain: 33; ascites: 35; transit disorder like diarrhea and constipation: 11). PCI improved in 64.5% of patients, 63.5% of patients presented with complete disappearance of symptoms. Major complications occurred as the outcome of 16 PIPAC (9.7%) and 5 (6.8%) patients died within 30 days of the PIPAC procedure. Rate of mortality and major complications 40% and 62% respectively occurred in first 20 treated patients. For 64 (88%) patients, systemic chemotherapy was associated with PIPAC and could be administered after PIPAC with a median delay of 14 days (2–28).

Conclusions

Implementing a PIPAC program in association with systemic chemotherapy is feasible and is associated with a risk of postoperative morbidity, even in teams highly experienced in PC management and requires a learning curve in patient selection.

Introduction

Peritoneal carcinomatosis (PC) is a common evolution of abdominal cancers and is associated with a poor prognosis in the absence of aggressive multimodal therapeutic approaches [1]. Since its origin in the 1990's, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been increasingly used as a curative treatment for PC [2], [3]. CRS and HIPEC offer the best outcome for pseudomyxoma peritonei and mesothelioma [4], [5] and represent the only current curative treatment for colorectal and gastric PC [6], [7]. For non-resectable PC, systemic chemotherapy is the only with limited effect on survival. With modern systemic chemotherapies associated with targeted therapies, expected median survival reaches 20 months for colorectal cancer [8], 17.6 months for ovarian cancer [9], 7 months for gastric cancer [10], and less than 12 months for peritoneal mesothelioma [11].

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an innovative intraperitoneal chemotherapy approach that seems to enhance the effect of chemotherapy by taking advantage of the physical properties of aerosol and pressure [12]. PIPAC is reported to be safe and well tolerated, with no postoperative hepatic and renal toxicities [13], [14], [15], [16], [17]. The first evidence for the efficacy of PIPAC was promising and reported regression of PC in tumors resistant to systemic chemotherapy [12]. In recent Systematic review, median survival after PIPAC was 13.4–15.4 months for gastric, 11–14.1 months for ovarian, and 15.7 months for colorectal PC [16].

The aim of the present study was to analyze and report the initial experience of PIPAC in three experienced centers in the management of PC who began a PIPAC program in regard to feasibility and postoperative outcome.

Section snippets

Study design

A prospectively maintained multi-institutional peritoneal carcinomatosis database was queried to identify all patients who underwent PIPAC, between December 2015 and December 2016, for non-resectable PC in 3 French tertiary university hospitals experienced in PC management (Lyon Sud university hospital, Clermont-Ferrand university hospital and Montpellier Institute of Cancer). All centers follow the implantation training program for practical and safety procedures organized by Professor Reymond

Results

Seventy-three patients underwent PIPAC for non-resectable PC in the three expert centers (Table 1). The origins of the PC were colorectal, gastric, ovarian, malignant mesothelioma, pseudomyxoma peritonei or other for 20, 26, 13, 8, 1 and 5 patients, respectively. Before the first PIPAC cycle, 57 patients presented symptoms of PC (pain: 33; ascites: 35; transit disorders: 11). At the time of the first PIPAC cycle, median PCI was 19 (1–39). For 57 patients, systemic chemotherapy was performed

Discussion

In this retrospective series of 164 PIPAC procedures in 73 patients with initially non resectable PC, ascites and symptoms related to PC were decreased during the PIPAC program where PCI was improved in 64.5% of patients. Meanwhile, grade III and IV (CTCAE v4) postoperative major complications occurred only 9.7% of treated patients.

In the current literature, mortality associated with PIPAC reached up to 8.3% [20] and major complications occurred in 0–37% of patients [16]. This high mortality is

Conclusion

Implementing a PIPAC program with systemic chemotherapy is feasible and is associated with a risk of postoperative morbidity, even in teams highly experienced in PC management and requires a learning curve in patient selection. International consensus is mandatory to determine a standardized PIPAC protocol.

Disclosure

The authors report no conflicts of interest relevant to this article.

Conflict of interest

The authors declare that they have no competing interests.

Author's contribution

All persons who meet authorship criteria are listed as authors, and all authors certify that they have participated sufficiently in the work to take public responsibility for the content, including participation in the concept, design, writing, or revision of the manuscript.

Furthermore, each author certifies that this material or similar material has not been and will not be submitted to or published in any other publication.

Conception and design of the study: 09/12/2015.

End of acquisition of

Acknowledgements

The authors thank Dr. Michèle Vidal, Dr. Amélie Massardier-Pilonchery, Dr. Nicolas Vantard, Marlene Parisot, Nathalie Vocanson, Salima Zouaoui, Cecile Vidal, Sophie Bidault-Marqués and Carine Scata for their contributions to the implementation of the PIPAC approach.

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