Pressurized intraperitoneal aerosol chemotherapy (PIPAC) as a neoadjuvant therapy before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Ramy Girshally, Cedric Demtröder, Nurettin Albayrak, Jürgen Zieren, Clemens Tempfer, Marc A Reymond, Ramy Girshally, Cedric Demtröder, Nurettin Albayrak, Jürgen Zieren, Clemens Tempfer, Marc A Reymond

Abstract

Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel drug delivery system able to induce regression of peritoneal metastasis (PM) in the salvage situation. The aim of this study was to determine the clinical characteristics, tumor histology, and extent of disease of the patients having undergone cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) after "neoadjuvant" PIPAC.

Methods: This study was performed at a single institution, tertiary center. In a prospective registry, retrospective analysis was done. PIPAC indication was restricted to patients in the salvage situation who were not eligible for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Results: Nine-hundred sixty-one PIPAC sessions were successfully performed in 406 patients: 21 patients (5.2 %) were scheduled for CRS and HIPEC. Twelve of these patients had a low PCI (mean 5.8 ± 5.6). The remaining nine patients showed an advanced peritoneal disease (mean PCI 14.3 ± 5.3) at initial laparoscopy. After repeated PIPAC (mean number of cycles 3.5 ± 0.9), radiological tumor regression was observed in 7/9 patients and major histological regression was observed in 8/9 patients, so that secondary CRS and HIPEC became possible.

Conclusions: PIPAC might be used as a neoadjuvant therapy before CRS and HIPEC in order to improve the outcome of CRS and HIPEC, to select patients with chemosensitive, biologically favorable tumors, to extent the indications of CRS and HIPEC in the presence of diffuse small bowel involvement, and to reduce the extent of cytoreductive surgery.

Keywords: Cisplatin; Cytoreductive surgery; Doxorubicin; Hyperthermic intraperitoneal chemotherapy (HIPEC); Intraperitoneal chemotherapy; Peritoneal metastasis; Pressurized intraperitoneal aerosol chemotherapy (PIPAC).

Figures

Fig. 1
Fig. 1
Indications for PIPAC (a1), for CRS and HIPEC (b) for CRS and HIPEC after “neoadjuvant” PIPAC (a2). In our institution, primary indications for PIPAC and HIPEC are relatively similar with a majority of ovarian cancers. However, indication for PIPAC was 12× more frequent than indication for CRS and HIPEC. Secondary CRS and HIPEC were performed in 5.1 % of PIPAC patients with a majority of colorectal cancer patients. PIPAC might allow secondary CRS and HIPEC in selected patients with colorectal cancer who were not eligible primarily for such procedure
Fig. 2
Fig. 2
Contrast-enhanced CT scans of a 57-year-old male patient with peritoneal metastasis of an appendiceal cancer. a Image after 12 cycles of combination palliative chemotherapy with FOLFOX4 and 6 cycles of FOLFIRI showing active disease with massive ascites (asterisk). b Evolution after 5 cycles of PIPAC with low-dose cisplatin and doxorubicin showing partial tumor response according to RECIST 1.1 criteria, in particular ascites control. c Postoperative image after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). d CT scan 6 months after CRS and HIPEC showing beginning recurrence (minimal ascites and tumor node on the lateral liver surface). The patient survived 46 months after diagnosis, 25 months after first PIPAC, and 18 months after CRS and HIPEC
Fig. 3
Fig. 3
Overall survival of 53 patients treated with CRS and HIPEC, grouped according to the organ of origin. Best survival is observed in pseudomyxoma peritonei patients (n = 9), followed by ovarian (n = 15) and colorectal (n = 19) cancer patients. In this retrospective cohort, selected patients with gastric cancer (n = 6) and malignant mesothelioma (n = 4) have the worst prognosis
Fig. 4
Fig. 4
Overall survival of 19 patients with peritoneal metastasis treated with CRS and HIPEC, with (green curve) or without (blue curve) “neoadjuvant” PIPAC. As expected, patients primarily not eligible for CRS and HIPEC and treated with neoadjuvant PIPAC seem to have a worse prognosis than the other patients. However, this difference does not reach statistical significance in this small cohort of patients

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