Complete cytoreductive surgery plus HIPEC for peritoneal metastases from unusual cancer sites of origin: results from a worldwide analysis issue of the Peritoneal Surface Oncology Group International (PSOGI)

<p><b>Aim:</b> The aim of this study was to assess the outcomes of patients operated on for peritoneal metastases from unusual cancer sites of origin, meaning apart from peritoneal metastases (PM) from colorectal, gastric and epithelial ovarian carcinomas, pseudomyxoma peritonei and mesothelioma.</p> <p><b>Patients and methods:</b> A questionnaire concerning patients treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for PM arising from unusual cancer sites of origin was sent to all centres, which routinely performed HIPEC, through the Peritoneal Surface Oncology Group International and the RENAPE network.</p> <p><b>Results:</b> Between September 1990 and June 2016, 850 procedures for unusual cases were performed in 781 patients, in 53 centres worldwide. Nearly two-thirds of the procedures were performed for three indications: rare ovarian carcinoma (<i>n</i> = 224), sarcoma (<i>n</i> = 189) and neuroendocrine tumours (<i>n</i> = 127). The median PCI was 12 [0–39]. Grade III–IV postoperative complications occurred in 272 patients (41%). Nineteen patients (2.9%) died postoperatively. After a median follow-up of 46 months, median overall survival (OS) was 39 months [33.18–44.05]. Five-year OS rate was 38.7%. For the three main indications, 5-year OS was significantly greater in patients with PM from rare ovarian carcinoma (57.7%), than that of patients with PM from neuroendocrine tumours (39.9%), and from sarcoma (29.3%) (<i>p</i> < 0.0001).</p> <p><b>Conclusions:</b> CRS and HIPEC appear to be safe and effective in patients with peritoneal metastases from unusual cancer sites of origin, especially from rare ovarian carcinomas, PM from neuroendocrine tumours. The respective roles of CRS and HIPEC remain unclear and should be evaluated.</p

Correlations of LA and AA levels (as masses or percentages of total FA) in malignant breast tissue, normal breast tissue, RBC, and plasma with the levels of 13-HODE, PGD₂ and PGE₂ in malignant breast tissue.

1<p>Pearson correlation coefficients between the cited FAs and metabolites. None of the correlations attained statistical significance. There were also no significant correlations between the FA in patients with >20 Mib1 scores (data not shown).</p

Metabolites and other markers.

<p>Malignant tissue levels of the indicated metabolites were compared for poorer or better prognoses by mitosis, nuclear pleomorphism, and tubule formation indices (panel A) or nodal metastasis (panel B). 13-HODE (panel C) and PGE₂ (panel D) levels were compared by poorer vs. better prognoses for: race, African (closed bars) or Caucasian American (open bars); Her2 score, 2 & 3 (closed bars) or 0 & 1 (open bars); age >50 years (closed bars) or ≤50 years (open bars); body mass index (BMI) >30 (closed bars) or ≤30 (open bars); estrogen receptors (ER) negative (closed bars) or positive (open bars); triple negative (tri (−)) for estrogen, progesterone, & Her2 receptors (closed bars) or not (open bars); tumor size, >2 (closed bars) or ≤ 2 cm (open bars). p Values are from Students t-test corrected for the 3 comparisons in each component of growth (panel A), for the 7 metabolite comparisons (panel B), or for the 7 marker comparisons (panels C and D) by the false discovery rate method. Analysis of these two metabolites for progesterone receptors or for 15-HETE, 12-HETE, 5-HETE, 5-oxo-ETE, and PGD₂ in all 8 marker categories found no significant differences (data not shown).</p

FA and Mib1.

<p>Levels of the indicated FA are presented as mass (upper panels) or percentage of total recovered FA (lower panels) in malignant (left panels) and normal (right panels) breast tissue of patients with high or low Mib1 scores. Comparison of the 7 FA parameters on the basis of high or low Mib1 score by Students t-test gave no significant differences even before correction for multiple comparisons; the same analysis in RBC and plasma likewise revealed no significant differences as a function of Mib1 scores (results not shown).</p

Molecular weights of the precursor and product ions⁻¹ of the metabolites and their deuterated internal standards selectively monitored by LC-tandem MS.

a<p>Internal standard for PGE₂ and PGE_3.</p>b<p>Internal standard for 5-HETE and 5-HEPE.</p

Metabolites and Mib1.

<p>Levels of the metabolites are compared by tissue type (panel A), Mib1 score in malignant (panel B) or normal (panel C) tissue; and grade in malignant tissue (panel D). Probability values were defined by paired (panel A) or unpaired (panels B, C, and D) Student t-tests and were corrected for the 7 comparisons made in each panel by the false discovery rate method.</p