Abstract
Simple SummaryPancreatic ductal adenocarcinoma (PDAC) with peritoneal dissemination is a highly lethal disease. Recently, promising activity of intraperitoneal chemotherapy with paclitaxel (i.p.-PTX) has been observed in patients with peritoneal dissemination. We conducted a retrospective comparative study to evaluate the clinical efficacy of i.p.-PTX combined with systemic chemotherapy versus standard systemic chemotherapy in PDAC patients with peritoneal dissemination. The median survival time was 10.2 months for patients in the standard therapy group and 17.9 months in the i.p.-PTX group; the difference between groups was statistically significant (p = 0.006). We have performed surgical resection (defined as conversion surgery) to responders to treatment. Conversion surgery was planned for 26% in the i.p.-PTX group and 8% in the standard therapy group. The median survival time (27.4 months) from initial treatment in patients who underwent conversion surgery was significantly longer than that in patients who did not undergo conversion surgery (11.3 months, p < 0.0001). Implementation of the i.p.-PTX regimen may improve survival in patients with PDAC with peritoneal dissemination.Background: Intraperitoneal chemotherapy using paclitaxel (i.p.-PTX) is expected to be a new therapeutic strategy for patients with pancreatic ductal adenocarcinoma (PDAC) and peritoneal dissemination. We evaluated the survival benefit of i.p.-PTX compared with standard systemic chemotherapy. Methods: Clinical data of 101 consecutive PDAC patients with peritoneal dissemination between 2007 and 2018 were analyzed. All patients were determined to have no other sites of distant organ metastasis to the lung, bone, or liver on contrast-enhanced CT imaging. Patients underwent staging laparoscopy or open laparotomy to confirm pathological evidence of peritoneal dissemination, and to exclude occult liver metastasis. Survival curves were estimated using the Kaplan–Meier method, and differences were compared using the log-rank test. Results: Forty-three patients were treated with i.p.-PTX (i.p.-PTX group) and forty-nine patients received standard systemic chemotherapy (Ctrl group). Nine patients did not receive any treatment (BSC group). The median survival time (MST) in the i.p.-PTX group was significantly longer than that in the Ctrl group (17.9 months vs. 10.2 months, p = 0.006). Negative peritoneal washing cytology was observed in 24 out of 43 patients in the i.p.-PTX group. The i.p.-PTX group tended to have a higher proportion of clinical responses than the Ctrl group (30% vs. 18%, p = 0.183). Conversion surgery was performed in 10 patients in the i.p.-PTX group and 2 patients in the Ctrl group after confirming disappearance of peritoneal dissemination with staging laparoscopy or open laparotomy (p = 0.005). The MST in patients who underwent surgical resection was significantly longer than that in patients who did not (27.4 months vs. 11.3 months; p < 0.0001). Conclusion: i.p.-PTX therapy provided improved survival in PDAC patients with peritoneal dissemination, and conversion surgery enhanced it in patients with favorable responses to chemotherapy. i.p.-PTX might become one of the treatment options to PDAC patients with peritoneal dissemination.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a close association between incidence and mortality within 1 year
Univariate analysis revealed that i.p.-PTX, clinical response, and conversion surgery were significantly associated with survival (Table 2)
The median survival time (MST) of metastatic pancreatic cancer is still less than 1 year
Summary
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a close association between incidence and mortality within 1 year. Peritoneal dissemination may be clinically divided into occult type diagnosed incidentally during open laparotomy or staging laparoscopy, and radiological detection type showing the presence of massive ascites, omental cake, intestinal obstruction, hydronephrosis [8,9], and concomitant organ metastases on imaging The former is primarily asymptomatic, but 60–80% of patients have been reported to suffer from ascites within 1 year after initial treatment (MST: 7–10 months) [10,11]. A preliminary report from our institution comparing clinical outcomes between intraperitoneal and systemic chemotherapy has been published: our retrospective study revealed that implementation of the S-1 plus intraveous/i.p.-PTX regimen (n = 20) was closely associated with prevention of ascites and higher resectability, Cancers 2022, 14, 1354 resulting in improvement of OS in chemotherapy-naive patients with PDAC with peritoneal metastasis, relative to 29 patients who received standard systemic chemotherapy [13]. We conducted a retrospective comparative study in a single institution to evaluate the clinical efficacy of i.p.-PTX combined with systemic chemotherapy versus standard systemic chemotherapy in PDAC patients with peritoneal dissemination but without other distant organ metastasis on a large scale
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