Benjamin L. Green, MD
Research Fellow
NCI
Bethesda, Maryland, United States
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
The peritoneum is the most common site of metastasis for advanced gastric adenocarcinoma (GA), yet there are no approved locoregional therapies to target peritoneal spread. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) represents a potential treatment for advanced GA with isolated peritoneal metastasis.
Methods: Interim results were analyzed from two separate single-institution phase II, single-arm studies evaluating CRS-HIPEC using cisplatin with mitomycin C (institution 1) or cisplatin, mitomycin C, and paclitaxel (institution 2) in patients with GA and confirmed peritoneal metastasis (NCT03092518 and NCT02891447). Clinical and pathologic variables, and surgical complications were evaluated by log-rank analysis with respect to the primary endpoint of overall survival (OS). Select patients underwent next-generation sequencing (NGS) of the primary tumor for pathogenic mutations.
Results: Over 4 years, a total of 42 patients were treated with CRS-HIPEC (18 from institution 1, 24 from institution 2 with 4 treated off-trial). All patients had synchronous peritoneal metastases and received systemic chemotherapy previously. Patients from institution 2 also received laparoscopic HIPEC prior to open CRS-HIPEC. The majority (64%, n=27) were male, and median PCI at CRS-HIPEC was 4. Median OS was 24.9 months post-diagnosis and 14.4 months from date of CRS-HIPEC. Three-year OS was 25% from diagnosis and 22% postoperatively. Median recurrence-free survival was 7.4 months. Multivariate analysis identified the number of positive lymph nodes as an independent predictor of postoperative OS. The rate of 30-day postoperative complications (Clavien-Dindo grade > 3) was 31% and rate of anastomotic leak was 21%. NGS analysis failed to demonstrate a molecular signature that was predictive of survival.
Conclusions:
In selected patients with GA, the number of pathologic lymph node metastases was inversely correlated with OS. This predictor, and the rate of major complications, supports a selective approach based on clinical variables related to nodal positivity and morbidity.