Safety of patients undergoing radical resection combined with paclitaxel-based hyperthermic intraperitoneal chemotherapy for locally advanced gastric cancer

Abstract

Objective: To analyze the safety of paclitaxel-based, hyperthermic, intraperitoneal perfusion chemotherapy (HIPEC) after radical resection of locally advanced gastric cancer. Methods: This was a retrospective cohort study of clinicopathological data of 467 patients with locally advanced gastric adenocarcinoma who had been admitted to the Department of Gastrointestinal Surgery, West China Hospital, Sichuan University between July 2019 and April 2021. Among these patients, 151 had undergone radical resection combined with post-operative paclitaxel-based HIPEC (surgery+HIPEC group) and 316 radical resection alone (surgery group). The adverse perioperative events in study patients were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0) published by the U.S. Department of Health and Human Services. Subgroup analysis was performed on patients in the surgery+HIPEC group according to the number of times HIPEC was administered and the incidence of adverse events was compared between subgroups using the χ2 test. Independent risk factors for paclitaxel-based HIPEC-associated adverse events were identified by applying a logistic model. Results: In the surgery+HIPEC group, there were 113 (74.8%) male and 38 (25.2%) female patients of median age 64 (55, 68) years, 18 (11.9%), 79 (52.3%), and 54 (35.8%) of whom had undergone one, two, and three paclitaxel-based HIPEC treatments, respectively, after surgery. The median maximum tumor diameter was 5.0 (3.6, 6.5) cm. In the surgery group, there were 244 (77.2%) male and 72 (22.8%) female patients of median age 63 (54, 68) and the median maximum tumor diameter was 4.0 (3.0, 5.5) cm. In the surgery+HIPEC group, 112 patients (74.2%) had 198 Grade 2 or higher adverse perioperative events, postoperative hypoalbuminemia being the commonest (85 cases, 56.3%), followed by postoperative anemia (50 cases, 33.1%). Compared with the surgery group, the incidences of postoperative hypoalbuminemia (56.3% [85/151] vs. 37.7% [119/316], χ2=14.420, P<0.001), anemia (33.1% [50/151] vs. 22.5% [71/316], χ2=6.030, P=0.014), abdominal pain [7.3% [11/151] vs. 1.6% [5/316], χ2=10.042, P=0.002) and abdominal distension (5.3% [8/151] vs. 1.3% [4/316], χ2=5.123, P=0.024) were all significantly higher in the surgery+HIPEC group. Analysis of the three HIPEC subgroups revealed significant differences in the incidences of postoperative hypoalbuminemia (13/18 vs. 67.1% [53/79] vs. 35.2% [19/54], χ2=12.955, P<0.001) and pulmonary infection (6/18 vs. 6.3% [5/79] vs. 1.9% [1/54], χ2=13.232, P<0.001) between them. Univariate analysis identified body mass index, Borrmann's type and number of HIPEC treatments as associated with perioperative adverse events in the surgery+HIPEC group (P<0.05). However, according to multifactorial logistic analysis, the above factors were not independent risk factors for perioperative adverse events in the surgery+HIPEC group (P>0.05). Conclusions: Paclitaxel-based HIPEC after radical resection significantly increases the risk of postoperative hypoalbuminemia, anemia, abdominal pain, and abdominal distension in patients who have undergone excision of locally advanced gastric cancer. However, increasing the frequency of HIPEC treatments did not significantly increase the risk of paclitaxel-based HIPEC-related adverse events. Moreover, univariate and multivariate analysis did not identify any independent risk factors for paclitaxel HIPEC-related adverse events.