Immune Effects of M51R Vesicular Stomatitis Virus Treatment of Carcinomatosis From Colon Cancer.

BACKGROUND: The purpose of this study was to analyze the oncolytic and immunomodulatory functions of an M protein mutant of vesicular stomatitis virus (M51R VSV) in a murine model of peritoneal surface dissemination from colon cancer (PSD from CRC). METHODS: Luciferase-expressing CT26 peritoneal tumors were established in Balb/c mice to evaluate the impact of M51R VSV treatment on intraperitoneal tumor growth and overall survival. The mice were treated with either intraperitoneal phosphate buffered saline (n = 10) or 5 × 106 PFU M51R VSV (n = 10) at 5 d after tumor implantation. Tumor bioluminescence was measured every 3 d during the 60-day study period. The immunomodulatory effect of M51R VSV treatment was evaluated in mice treated with either intraperitoneal phosphate buffered saline (n = 21) or M51R VSV (n = 21). Peritoneal lavages were collected at days 1, 3, and 7 after M51R VSV treatment for flow cytometry and multiplex cytokine bead analysis. RESULTS: A single, intraperitoneal treatment with M51R VSV inhibited the growth of PSD from CRC as evidenced by decreased bioluminescence and improved survival. This treatment approach also resulted in significantly higher frequencies of peritoneal CD4+ T (10.95 ± 1.17 versus 6.19 ± 0.44, P = 0.004) and B1b cells (5.01 ± 0.97 versus 2.20 ± 0.2, P = 0.024). On the other hand, treatment with M51R VSV resulted in fewer myeloid-derived suppressor cells relative to controls (10.66 ± 1.48 versus 14.47 ± 1.06, P = 0.035). M51R-treated peritoneal cavities also contained lower concentrations of immunosuppressive monocyte chemoattractant protein-1 and interleukin 6 cytokines relative to controls. CONCLUSIONS: Our findings suggest that M51R VSV alters the innate and adaptive immune responses in PSD from CRC. Future studies will delineate specific components of antitumor immunity that result in its therapeutic effect.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in sarcomatosis from gastrointestinal stromal tumor.

The role of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) procedures in the management of patients with gastrointestinal stromal tumor (GIST)-induced sarcomatosis that is refractory to tyrosine kinase inhibitors (TKI) is not well defined. A retrospective analysis of a prospective database of 1070 CRS/HIPEC procedures was performed. Demographics, Eastern Cooperative Oncology Group performance status, resection status, morbidity, mortality, perioperative use of targeted therapies, and overall survival were analyzed. Since 1992, 18 CRS/HIPEC procedures were performed for peritoneal dissemination of GIST. Fifty per cent of these cases were performed before the introduction of TKIs. R0/1 resection was achieved in 72 per cent, whereas 63 per cent of patients were treated with neoadjuvant and/or adjuvant targeted therapy. Thirty-day morbidity and mortality were 33.3 and 5.6 per cent, respectively. Median overall survival after CRS/HIPEC was 3.33 years with 3-year survival of 56 per cent. Median survival in those who did not receive targeted therapy was 1.04 versus 7.9 years for those treated with TKI and cytoreduction. Median postsurgical survival for those treated preoperatively with progression on TKI treatment was 1.35 years versus not reached in those on TKI therapy without progression. Primary therapy for patients with disseminated GIST should be TKI therapy. However, in patients with sarcomatosis from GIST, cytoreduction should be considered before developing TKI resistance. Progression on TKI is associated with poor outcomes even after complete cytoreduction.