Complete CRS-HIPEC with cisplatin is effective in select DSRCT patients. DSRCT patients with hepatic or portal metastasis have poorer outcomes.

Purpose The clinical effects of sunitinib on human myeloid-derived suppressor cell (MDSC) subsets and correlation of the T-cell–mediated immune responses and clinical outcomes in patients with oligometastases treated by stereotactic body radiotherapy (SBRT) have been evaluated. Experimental Design The numbers of granulocytic and monocytic MDSC subsets, effector T cells, and regulatory T cells in the peripheral blood were evaluated pre- and post-sunitinib treatment and concurrent with SBRT. Correlations between MDSC, Treg, and T-cell responses and clinical outcomes were analyzed. Results Patients with oligometastases of various cancer types had elevated granulocytic MDSC and certain subsets of monocytic MDSC population. Sunitinib treatment resulted in a significant reduction in monocytic MDSC, phosphorylated STAT3, and arginase levels in monocytic MDSC (CD33+CD14+CD16+), and an increase in T-cell proliferative activity in cancer patients. Interestingly, the effects of sunitinib on reducing the accumulation and immune-suppressive function of MDSC were significantly correlated with Treg reduction, in responders but not in nonresponding patients. SBRT synergized the therapeutic effects of sunitinib, especially as related to decreased numbers of monocytic MDSC, Treg, and B cells, and augmented Tbet expression in primary CD4 and CD8 T cells. These effects were not observed in patients receiving radiation therapy alone. Most interestingly, the responders, defined by sunitinib-mediated reduction in CD33+CD11b+ myeloid cell populations, tend to exhibit improved progression-free survival and cause-specific survival. Conclusions Sunitinib treatment increased the efficacy of SBRT in patients with oligometastases by reversing MDSC and Treg-mediated immune suppression and may enhance cancer immune therapy to prevent tumor recurrence post-SBRT.

One of the several impediments to effective oncolytic virus therapy of cancer remains a lack of tumor-specific targeting. Myeloid derived suppressor cells (MDSCs) are immature myeloid cells induced by tumor factors in tumor-bearing hosts. The biodistribution kinetics of MDSC and other immune cell types in a murine hepatic colon cancer model was investigated through the use of tracking markers and magnetic resonance imaging (MRI). MDSCs were superior to other immune cell types in preferential migration to tumors in comparison to other tissues. Based on this observation, we engineered a strain of vesicular stomatitis virus (VSV), an oncolytic rhabdovirus, that bound MDSCs and used them as a delivery vehicle. Improving VSV binding efficiency to MDSCs extended the long-term survival of mice bearing metastatic colon tumors, compared to systemic administration of wild-type VSV alone. Survival was further extended by multiple injections of the engineered virus without significant toxicity. Notably, direct tumor killing was accentuated by promoting MDSC differentiation towards the classically activated M1-like phenotype. Our results offer a preclinical proof of concept for using MDSCs to facilitate and enhance the tumor-killing activity of tumor-targeted oncolytic therapeutics.

Importance: Dynamic computed tomography (CT) is emerging as a first-line alternative to sestamibi scintigraphy for preoperative localization of parathyroid lesions. In recent years, there has been increased concern over the impact of radiation exposure from medical imaging, as well as on the cost of diagnostic medical procedures. An ideal diagnostic procedure would be cost effective while minimizing hazardous exposures and complication rates.Objective: To compare the radiation dose and financial cost of dynamic CT with sestamibi scintigraphy. Main Outcomes and Measures:The 2 primary study outcomes were radiation exposure measured in millisieverts (mSv) and medical charges for the respective diagnostic procedures. The study was conducted with the hypothesis that dynamic parathyroid CT would have slightly greater radiation exposure with similar cost to sestamibi scintigraphy.Results: Dynamic parathyroid CT and sestamibi scintigraphy delivered mean radiation doses of 5.56 and 3.33 mSv, respectively (P Ͻ .05). Charges totaled $1296 for thin-cut dynamic parathyroid CT and a mean of $1112 for sestamibi scintigraphy, depending on the type and amount of radiotracer injected. Although multiphase CT scanning took less than 5 minutes, sestamibi scintigraphy lasted a mean time of 306 minutes. A total of 62 of 119 patients (52%) in the CT group have undergone operative treatment to date, whereas all patients in the sestamibi arm underwent operative treatment of their hyperparathyroidism. Of the patients who underwent a surgical procedure, CT correctly identified the side of the parathyroid adenoma in 54 of 62 patients (87%), while sestamibi scintigraphy only correctly lateralized 90 of 122 adenomas (74%) as confirmed by exploratory surgery, intraoperative parathyroid hormone levels, and pathologic features. A dynamic parathyroid CT correctly predicted multiglandular disease in 1 of 7 patients (14%), while sestamibi scintigraphy correctly predicted multiglandular disease in 8 of 23 patients (35%). Conclusions and Relevance:In patients who underwent directed parathyroid surgery, dynamic CT is comparable to sestamibi scintigraphy in patients with hyperparathyroidism. Although CT delivers a higher dose of radiation, the average background radiation exposure in the United States is 3 mSv/y, and added exposures of less than 15 mSv are considered low risk for carcinogenesis. Overall, dynamic parathyroid CT is a safe, cost-effective alternative to sestamibi scintigraphy.

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