Reproducibility of the peritoneal regression grading score for assessment of response to therapy in peritoneal metastasis.

The four-tiered peritoneal regression grading score (PRGS) assesses the response to chemotherapy in peritoneal metastasis (PM). The PRGS is used, for example, to assess the response to pressurised intraperitoneal aerosol chemotherapy (PIPAC). However, the reproducibility of the PRGS is currently unknown. We aimed to evaluate the inter- and intraobserver variability of the PRGS. Thirty-three patients who underwent at least three PIPAC treatments as part of the PIPAC-OPC1 or PIPAC-OPC2 clinical trials at Odense University Hospital, Denmark, were included. Prior to each therapy cycle, peritoneal quadrant biopsies were obtained and three haematoxylin and eosin (H&E)-stained step sections were scanned and uploaded to a pseudonymised web library. For determining interobserver variability, eight pathologists assessed the PRGS for each quadrant biopsy, and Krippendorff's alpha and intraclass correlation coefficients (ICCs) were calculated. For determining intraobserver variability, three pathologists repeated their own assessments and Cohen's kappa and ICCs were calculated. A total of 331 peritoneal biopsies were analysed. Interobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was moderate to good/substantial. The intraobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was good to excellent/almost perfect. Our data support the PRGS as a reproducible and useful tool to assess response to intraperitoneal chemotherapy in PM. Future studies should evaluate the prognostic and predictive role of the PRGS

Role of immunohistochemistry for interobserver agreement of Peritoneal Regression Grading Score in peritoneal metastasis.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC)-directed therapy is a new treatment option for peritoneal metastasis (PM). The 4-tiered Peritoneal Regression Grading Score (PRGS) has been proposed for assessment of histological treatment response. We aimed to evaluate the effect of immunohistochemistry (IHC) on interobserver agreement of the PRGS. Hematoxylin and eosin (H&E)-stained and IHC-stained slides (n = 662) from 331 peritoneal quadrant biopsies (QBs) taken prior to 99 PIPAC procedures performed on 33 patients were digitalized and uploaded to a web library. Eight raters (five consultants and three residents) assessed the PRGS, and Krippendorff's alpha coefficients (α) were calculated. Results (IHC-PRGS) were compared with data published in 2019, using H&E-stained slides only (H&E-PRGS). Overall, agreement for IHC-PRGS was substantial to almost perfect. Agreement (all raters) regarding single QBs after treatment was substantial for IHC-PRGS (α = 0.69, 95% confidence interval [CI] = 0.66-0.72) and moderate for H&E-PRGS (α = 0.60, 95% CI = 0.56-0.64). Agreement (all raters) regarding the mean PRGS per QB set after treatment was higher for IHC-PRGS (α = 0.78, 95% CI = 0.73-0.83) than for H&E-PRGS (α = 0.71, 95% CI = 0.64-0.78). Among residents, agreement was almost perfect for IHC-PRGS and substantial for H&E-PRGS. Agreement (all raters) regarding maximum PRGS per QB set after treatment was substantial for IHC-PRGS (α = 0.61, 95% CI = 0.54-0.68) and moderate for H&E-PRGS (α = 0.60, 95% CI = 0.53-0.66). Among residents, agreement was substantial for IHC-PRGS (α = 0.66, 95% CI = 0.57-0.75) and moderate for H&E-PRGS (α = 0.55, 95% CI = 0.45-0.64). Additional IHC seems to improve the interobserver agreement of PRGS, particularly between less experienced raters

Pressurized Intra Peritoneal Aerosol Chemotherapy in patients suffering from peritoneal carcinomatosis of pancreatic adenocarcinoma

Patients suffering from peritoneal carcinomatosis of pancreatic adenocarcinoma were treated with Pressurized Intra Peritoneal Aerosol Chemotherapy (PIPAC), initial clinical findings are presented.Single institution, tertiary referral center certified for therapy of peritoneal disease. Prospective data collection of PIPAC therapy with doxorubicin 1.5 mg/m2 and cisplatin 7.5 mg/m2 of body surface delivered at intervals of six weeks. The outcome criteria were microscopic pathological response, survival and adverse events (v4.0 CTCAE).A total of 20 patients (m/f = 3:1) with a mean age of 64.9 (range: 45.0 to 87.0) years underwent 41 PIPAC procedures without intraoperative complications. The mean number of PIPAC cycles was 2.1 (range: one to four). Ten patients with ≥ 2 PIPAC applications were eligible for histological analysis to assess carcinoma regression. Complete or high grade tumor regression was found in two (10%) and five (25%) patients, respectively. An overall median survival of 36.6 weeks after the first PIPAC application was observed. One patient died postoperatively due to small bowel obstruction. No CTCAE level 3 and 4 complications occurred.In about one third of patients, repeated PIPAC therapy did induce histological regression of systemic chemo-resistant PC of pancreatic adenocarcinoma. Prospective randomized trials are needed to further clarify any clinical impact of such observations